Biographical Memoirs: Volume 56 (1987)

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VINCENT DU VIGNEAUD May ~ 8, ~ 901-December ~ I, ~ 978 BY KLAUS HOFMANN VINCENT DU VIGNEAUD was born in Chicago in 1901. He was of French ancestry, the son of Alfred du Vig- neaud, an inventor and machine designer, and Mary Theresa du Vigneaud. He attended Car! Schurz High School in Chi- cago, from which he graduated in 1918. When he was a freshman in high school, two friends, who had a chemical laboratory at home, invited him to join them in chemical ex- perimentation. They obtained chemicals from a pharmacist and conducted experiments that involved the fabrication of explosives containing sulfur. This was his first contact with science. World War I was under way, and young people were needed on the farms. Seniors in high school were offered the opportunity of working on the farms in spring and receiving their diplomas in tune. Young Vincent worked through spring and summer on a farm near Caledonia, Illinois. He was very proud of the fact that he could milk twenty cows by hand, and he decided to become a farmer. His older sister, Beatrice, changer] his mind and suggested that he go to the University of Illinois at Urbana-Champaign to study chem- istry. He followed her advice and registered in chemical en- gineering. He later recalled: 543

544 BIOGRAPHICAL MEMOIRS I found during the first year that it was chemistry rather than engi- neering that appealed to me most. I switched to a major in chemistry since I was deeply impressed by the senior student's work, especially in organic chemistry. I also found that I was most interested in those aspects of or- ganic chemistry that had to do with m~rlir~1 cilhst~nc~s anal heron to rl~ velop an interest in biochemistry. Young flu Vigneaud had no money and had to put himself through college and graduate school. Tearing clown boilers, picking apples, working in the library, and jerking sodas were some of his occupations. But the job that helped most finan- cially was that of headwaiter. The next most remunerative job turned out to be the teaching of cavalry tactics and equi- tation as a reserve second lieutenant in the cavalry. One clay, while working as a waiter, Vincent saw a pretty rec~head and said to one of his colleagues, "That's the woman ~ am going to marry" and he clict. The young woman was ZelIa Zon Forct. She was an English major, but as she and Vincent became better acquainted he saw to it that she took classes in mathematics and chemistry. Although she gradu- atect as an English major, she knew sufficient chemistry so that after their marriage on June 12, 1924, she was able to teach chemistry in high school. One of the professors at Illinois who exerted a significant influence on young (lu Vigneaud was Car! Shipp Marvel, known as "Speect." Du Vigneauc] was much impressed with Marvel's lectures and research program, and he decided to do his senior thesis with him. Later he selectee! Speed to be- come his master's degree adviser. As he progressed with his studies, he became more and more interested! in the relations between biochemistry and organic chemistry. He took acI- vancect courses in biochemistry from H. B. Lewis and the nutritionist W. C. Rose, whose studies on nutrition of the white rat later became role models for some of clu Vigneaucl's metabolic investigations. He was particularly taken with a lec

VINCENT DU VIGNEAUD 545 ture by Professor Rose in which the work of Banting and Best on insulin was cliscussed. Du Vigneauc! earnest his master's degree in February of 1924 anc! accepted a position with the Du Pont Company; he later worked for some time with Dr. Walter Karr at the Phil- adelphia General Hospital. Nevertheless, his minct was set on graduate study and the earning of a Ph.D. degree. Professor Marvel recalls the following episode: When du Vigneaud received his master's degree he was offered a job with Walter Karr in Philadelphia, but he was too poor and had no money to pay his way to Philadelphia. To help him out I gave him an assignment to make 10 pounds of cupferron for our organic preparations laboratory and told him I would pay him, as a wage, whatever amount he could pro- duce in material for under the price which we would sell it. He did not ask for any hourly work or time, but we generally agreed that way. In pro ducing the 10 pounds, he'd accumulated enough money to get to his Phil- adelphia job. In the spring of 1925 do Vigneauct received an invitation from Professor John R. Murlin to join the Department of Vital Economics at the University of Rochester, New York, to undertake graduate work on the chemistry of insulin. Pro- fessor Murlin was a physiologist and not a chemist, and du VigneaucI was eager to discuss his chemical problems with other chemists. In this connection, he became acquainted with Hans Clarke, who at the time was working for Eastman Kodak. Later, Clarke became professor and chairman of the Biochemistry Department at the College of Physicians and Surgeons in New York, and the two men struck up a lifelong friendship. In 1927 clu Vigneauc! graduated with a Ph.D. clegree; the thesis title was "The Sulfur in Insulin." During his last year in Rochester he was awardecl a National Research Council Fellowship, which enabled him to pursue postdoctoral stucl- ies with John Jacob Abel, professor of pharmacology at the

BIOGRAPHICAL MEMOIRS . 546 Johns Hopkins University Medical School. Here, in colIabo- ration with Oscar Wintersteiner and Hans Jensen, the insulin studies were continued. A second fellowship enabled the young du Vigneaud to do some traveling abroad. He became acquainted with the synthesis of pepticles in the laboratory of Max Bergmann at the Kaiser Wilhelm Institut in Dresden and spent some time with Professor George Barger in Edin- burgh, ScotIanct. Bergmann, a former stud ent of Emil Fischer, was a pioneer in the peptide field who later became a member of the Rockefeller Institute for Medical Research (now Rockefeller University) in New York. Broadly equipped to engage in independent scientific pursuits, du Vigneaud accepted a position in the Department of Physiological Chemistry at his alma mater in Illinois. Bio- chemistry had become his chosen field, and the opportunity presented itself to have graduate students. He spent three happy years in Illinois; at age thirty-one he became professor and chairman of biochemistry at George Washington Uni- versity Meclical School in Washington, D.C. He was sacIdenect to leave the outstanding department at Urbana with such great professors as Adams, Marvel, Shriner, and Fuson in organic chemistry and Professor Rose in biochemistry, but the opportunity for greater inclepenclence was decisive. He stayed at George Washington from 1932 to 193S, when he was invited to head the Department of Biochemistry at Cornell Medical College in New York City, a chair that had been occupied by Stanley R. Ber~edict. In connection with this move he stated: When I came to Cornell Medical College, I brought along five mem- bers of my research group, Mildred Cohn, George W. Irving, Theodore Loring, Gail Miller, and John Wood. As in the transfer from Illinois to George Washington I thus had continuity, people with whom I had already been working. This I regard as very important when moving from one place to another. Just as in transplanting a tree with some soil around it, if possible it is well to move a man with some of his environment.

VINCENT DU VIGNEAUD 547 The awarding of the 1955 Nobel Prize in Chemistry con- stituted an unquestionable triumph for clu VigneaucI, but he expressed definite opinions pertaining to the awarding of prizes for scientific achievement. He saicI to a reporter, "l am expecting to stay in the research field, in the academic world, but ~ want to tell you ~ will never work for any prize. I refuse to let my rewards rest in the hands of any committee." In answer to a congratulatory note I sent him on the oc- casion of his award, he answered: "The real thrill of such an aware! is sharing the pleasure with one's friends, and partic- ularly with those who have been associated with me on the trail." The highly productive career at Cornell Medical College came to an enct with his assumption of emeritus status in 1967. But a generous invitation from Professor HaroIc! A. Scheraga, then head of the Chemistry Department at Cornell University in Ithaca, made it possible for du Vigneauct to continue his investigations as professor of chemistry. He was very happy and productive in Ithaca and enjoyocl his new surroundings. He wrote to his former collaborators and stu- dents: "Those of you who know the Ithaca area will appre- ciate that ~ have a fantastic view from my office on the sixth floor of the Chemistry Research Building overlooking Ca- yuga Lake to the northwest anct Beebe Lake, waterfalls and the Fall Creek gorge down below." In addition to his outstanding contributions to science, do Vigneaud was a great teacher and lecturer. His lectures to students were interesting and well prepared. He emphasized the importance of teaching and his advice to the faculty was: "Remember your first obligation is teaching; when you are teaching it takes precedence over research." His presenta tions at home and abroad were masterpieces of staging. He wouIct go over his slicles with the projectionist in the greatest detail so that the presentation wouIc! proceec! flawlessly. He was a showman, an artist in communicating research find

548 BIOGRAPHICAL MEMOIRS ings. It was a genuine pleasure to listen to his presentations, which were as meticulously prepared and rehearsed as were . . . ~ . 11S sclentluc papers. Professor flu Vigneaucl's scientific career was abruptly ter- minatect when he sufferer! a stroke in 1974. He cried on De- cember ~ I, 1978. His wife, ZelIa, had passed away one year earlier. Professor du Vigneaud is survived by a son, Vincent, Jr., and a daughter, Marilyn Renee Brown. Both are physi- cians. If one views the totality of clu Vigneaucl's contributions to science, one recognizes a thread of continuity connecting sulfur-containing, biologically important compounds. This threact extends from insulin to cysteine, homocysteine, me- thionine, cystathionine, biotin, penicillin, oxytocin, and va- sopressin. In the Messenger lectures, delivered at Cornell University in Ithaca in 1950, he likened his scientific work to a trail in research; he wrote: An attempt was made to retrace the research trails originating from a study of insulin that I have had the pleasure of working out in association with various collaborators over a period of twenty-five years. I attempted to present not only the findings encountered, but also in many instances the stepwise evolution of these findings, including the accidents of fate that played a part. Some of flu Vigneaucl's earliest researches clealt with the chemical nature of insulin. Abe! crystallized insulin in 1926, ant] Jensen, Wintersteiner, and clu Vigneauc! investigated the composition of acid hydrolysates of the crystalline hormone. With the rather primitive methods available at the time, the presence in such hyctrolysates of cystine and various other amino acids was establishect. Based on this evidence, it was . concluder! that insulin was a protein. Du VigneaucI com- mented later: "It may seem strange to speak of work estab- lishing insulin as a protein because it is now a generally ac

VINCENT DU VIGNEAUD 549 ceptec! fact that a hormone can be a protein or that a protein can be a hormone, yet at that time (1928) there was great reluctance in accepting this viewpoint." The thinking at that time was strongly influences! by the concepts of WilIstatter regarding the chemical nature of enzymes that were assumed to be composed of a small functional coenzyme anti a protein carrier. Insulin was believed to be a small molecule that was attacher! or absorber! to a high molecular weight carrier. In 1930 clu Vigneaud became acquainted with L. F. Au- drieth, a faculty colleague at the University of Illinois, who was an expert in the liquid ammonia field. He was impressed with liquid ammonia as a solvent for insulin and the sparingly soluble cystine. Au~rieth's use of metallic sodium as a recluc- ing agent in liquid ammonia promptest du Vigneaucl to apply this method to the conversion of cystine to cysteine. He de- vised the technique of S-benzylation of cysteine by a(lding be n zy! chloride to sodium in l iqu icI ammo nia- reducer! cys- tine. The observation that the S-benzy! group was remover! from S-benzy~cysteine by reduction with sodium in liquid am- monia represented a significant contribution to peptide . . . -my, ~ me possible tne transient protection of the thio] group of cysteine during peptide syntheses. In 1932 Bergmann and Zervas introducec! the benzyloxy- carbony! group (carbobenzoxy group) into amino acids anti pepticles, and with the discovery that this protecting group could be cleavecI by catalytic hydrogenolysis they laicl the groundwork for the (development of modern pepti(le synthe- sis. Du Vigneaud became interested in this method ant! em- barkocI on synthesizing carbobenzoxy derivatives of amino acids. The story has it that in his laboratory the carboben- zoxyamino acids failed to crystallize. One clay, Max Berg- mann came to visit the laboratory anti, lo and behoIcI, from that time on the carbobenzoxyamino acids crystallized beau- tifully. Dic! Bergmann carry seer! crystals in his pockets? The ~1 ~ ~. ~ _ : ~1 _ 1 1 . 1 . -

550 BIOGRAPHICAL MEMOIRS discovery that benzyloxycarbonyl groups can be removed from cysteine and cysteine-containing peptides by sodium in liquid ammonia broadened the scope of the carbobenzoxy method and opened its applicability to peptides containing sulfur. As we proceed with this discussion, it will become appar- ent that the techniques du Vigneaud developed early in his career provided answers to problems he encountered at a later time (oxytocin and vasopressin). Much of du Vigneaud's work in intermediary metabolism concerned the formation of cysteine in the animal organism and the metabolic rela- tionships among methionine, cysteine, homocysteine, cysta- thionine, and choline. He called the underlying reactions "transulfuration" and "transmethylation." It was known that methionine could support growth of laboratory rats on a cys- teine-free diet, and Rose had shown that methionine was an essential dietary constituent for the rat. In short, the rat is capable of synthesizing cysteine but not methionine. In 193 ~ du Vigneaud discovered a new sulfur-containing amino acid while exposing methionine to strong sulfuric acid. This com- pound was the next higher symmetrical homolog of cystine and he named it "homocystine." Later, he ctiscovered that the reduced form of this amino acid, homocysteine, was a meta- bolically important compound. Du Vigneaud observed that homocysteine, like methionine, could support the growth of . ,~ . . . rats on c lets c Accent In costing. These observations pointed to a metabolic relationship between methionine and homocysteine and suggested that demethylation of methionine could be involved in cysteine biosynthesis. Du Vigneaud synthesized r-cystathionine, a thioether in which the carbon chains of cysteine and homo- cysteine are connected by a single sulfur atom, and found that this compound sustained growth of rats on a cysteine- deficient diet. This observation indicated that the rat was ca- pable of cleaving the thioether linkage with formation of cys

VINCENT DU VIGNEAUD 55 seine. It was observed further that cystathionine dicl not give rise to homocysteine, an observation that was supported by in vitro studies with liver slices. The acictition to liver slices of a mixture of homocysteine and serine resultect in a 60 per- cent conversion of homocysteine sulfur into cysteine, provict- ing strong evidence for the hypothesis that homocysteine was indeed! an intermediate in the formation of cystathionine. The importance of serine as a precursor of cysteine had been clemonstrated earlier by Dewitt Stetten. Before continuing the discussion of du Vigneaucl's work on the intermediary metabolism of sulfur compounds, it seems fitting to have a short synopsis of the status of bio- chemistry in the 1930s. At that time, the Biochemistry De- partment of the College of Physicians and Surgeons at Co- lumbia University, under the leaclership of Hans Clarke, had ctevelopect into one of the outstanding departments in the country and one that macle scientific history. It was in this department that Rudolf Schonheimer and his colleagues per- formed the classical tracer experiments pointing to "the cly- namic state of the body constituents." The application of iso- topes to the solution of biochemical problems provided the key for these clevelopments, which revolutionized biochemi- cal thinking. Harold C. Urey, also of Columbia University, had cleveloped the methoclology for the preparation of cleu- terium oxide and other elements enriched with respect to stable isotopes, anct the availability of these compounds opened far-reaching biochemical frontiers. Because growth experiments had severe limitations, du Vigneaud applied the new tracer techniques to the study of the conversion of me- thionine to cysteine. He synthesized D~-methionine labeler] in the ,B and By positions with ~3C and containing 34S and fed this compounc! to rats. The rats were shaved at the beginning of the experiment and received another haircut after thirty- eight days in the experiment. The cystine isolated from the hair contained 34S, but no i3C. From the results of this ex .

552 . BIOGRAPHICAL MEMOIRS percent it was concluclect that only the sulfur, not the carbon chain of methionine, was utilizect for cysteine biosynthesis. This proviclec! final proof that, in the rat, cysteine synthesis from methionine involves demethylation with formation of homocysteine followed by condensation of the homocysteine with serine to form cystathionine. The latter is cleaved with formation of cysteine anct c~-ketobutyric acid. In essence, the conversion of methionine to cysteine involves a transfer of the methionine sulfur to serine. This, according to du Vig- neaud, became known as "transulfuration." An interesting coincidence led to the discovery of the con- cept of transmethylation or methyl transfer. Here again the crucial evidence was derived from rat feeding experiments. Rose observer! good growth of rats fed a methionine- cysteine-free diet that was supplemented with homocysteine. Similar experiments carried out in du Vigneauct's laboratory produced negative results; the rats failecT to grow. The ani- mals in both laboratories grew well when the diet was forti- fiec! with methionine. The difference in the results was traced to the vitamin supplements used. Du Vigneau(1 employe(1 crystalline B complex vitamins, but Rose used rice bran ex- tract (Tikitiki) as the vitamin source. Du Vigneaud notect that his rats developed fatty livers while on experiment. It was known from the work of Best that choline inhibited fatty infiltration of the liver, and Du Vigneaud reasoned that this pathology could be the result of a choline deficiency. He cle- cicled that the factor missing in his diet couIct be choline, and this proved to be correct. Accordingly, diets containing both homocysteine and choline were fecI, and such a regimen sup- portect growth as well as did methionine. On the basis of these findings du Vigneaud speculatecl that choline, a compound rich in methyl groups, couIcl act as a methyl donor for the conversion of homocysteine to me- thionine. These early findings led to the concept of trans- methylation and that of "labile" methyl groups. The obser

VINCENT DU VIGNEAUD 553 vation that rats grew well and failed to develop fatty livers on a choline-free diet supplemented with methionine suggeste(1 to du Vigneaud that the methionine could serve as a methyl source for choline synthesis. These concepts were amply confirmed by tracer experiments. Methionine in which the methyl group was enriched with respect to deuterium was fed to rats, and choline was isolated from the tissues. This choline contained deuterium in its methyl groups, demon- strating transmethylation from methionine. Conversely, cho- line containing cleuterium was given to rats, anct deuterium was present in the methyl group of methionine. Thus the hypothesis that methionine was biosynthesizect from homo- cysteine by a methyl transfer from choline was substantiated. It was also observed that the transfer of methyl groups was a continuous process. In addition, clu Vigneaud fount] that the methyl group of creatine was clerived from the methyl group of methionine. The transfer of methyl groups from methionine to choline and from choline to methionine is a reversible process, but the methyl group of creatine does not serve as a methyl donor for the conversion of homocysteine to methionine. Baser! on these studies, du Vigneaud con- cluclecI: From our study, we know only that the methyl group of methionine and choline can be transferred, but we do not know whether methionine or choline react directly or whether they are precursors of derivatives from which the methyl groups are released. Although methionine can be de- methylated in vitro, the conditions required are drastic. Attention must therefore be directed to any possibility whereby the bond between the methyl group and the sulfur atom may be weakened. The formation of a sulfonium ion would be expected to effect such a labilization. It remained for Cantoni to identify the methyl donor in bio- logical systems as the sulfonium ion S-adenosy~methionine. The work on biotin resultect from an invitation to du Vig- neaud from Paul Gyorgy to collaborate in establishing the cry chemical nature of the anti-egg-white injury factor in liver,

554 BIOGRAPHICAL MEMOIRS which Gyorgy had designated as vitamin H. Rats receiving diets containing large proportions of raw egg white as the source of protein develop severe dermatitis and nervous dis- orders and die if the condition is not relieved. Certain food- stuffs, such as liver and yeast, contain a substance capable of preventing and curing this disorder. The curative factor was named vitamin H by Gyorgy (H being (lerived from the Ger- man word Haul, meaning skin). Biotin, a yeast growth factor, had been isolated from egg yolks by Kog} and Tonnis. Du Vigneaud, Gyorgy, and collaborators were able to cure egg- white injury with Kog1's pure biotin, demonstrating that vi- tamin H and biotin were one and the same compound. Biotin was isolated from liver extracts and milk in the Cornell lab- oratories, and the chemical structure of the compound was established. The structure worked out by du Vigneaud and collaborators was verified by chemical synthesis in the Merck laboratories. Biotin, first discovered as a yeast growth factor, turned out to be a mammalian vitamin. The Second World War interrupted the operations of the laboratory, and du Vigneaud was invited by the wartime Committee on Medical Research, OSRD, to join the great effort being organized in this country and in England to work on the chemistry of penicillin. Many contributions to peni- cillin chemistry emanated from the Cornell laboratory. Per- haps the most outstanding were those dealing with the syn- thesis of minute quantities of the antibiotic and its ident- ification with the natural compound. One amusing sidelight to the penicillin story comes from Sofia Simmonds. During a discussion with Hans Clarke, she remarked that penicillin must contain sulfur. Hans Clarke, who was in charge of the U.S. part of the super-secret peni- cillin project, was shocked to hear this and he wanted to know how she'd found out. She said we all couIct tell; the labs on the second floor, where the work was being done, leaked ben

VINCENT DU VIGNEAUD 555 zylmercaptan into the hallway- any V du V person knew what that meant. Du Vigneaud's work on the posterior pituitary principles oxytocin and vasopressin was starter! in 1932 and continued unfit ~ 940, when it was interrupted by the Second Worlc! War. During this time, however, the emphasis of the laboratory was on the metabolic aspects, transulfuration and transmeth- ylation, and du Vigneauc! referred to his work with the pos- terior pituitary hormones as his hobby. Some progress had been made in purification of these principles, mainly by the use of precipitation and electrophoretic techniques, but of . . · · ~ prime importance were some pre Mary o ~servat~ons sug- gesting that oxytocin and vasopressin were derivatives of cys- tine. During the war, new techniques became available that hac! a critical effect on the progress of the posterior pituitary hormone project. Of immediate importance were the Craig countercurrent distribution published in 1944 and the starch column technique of Moore anti Stein for the quantitative separation of mixtures of amino acids in acid hydrolysates of · . proteins on a micro sca e. Du Vigneaud returned to the study of the posterior pi- tuitary principles in 1947. A concentrate he had receiver! from Parke-Davis in 1940 that was stored during the war years was reassayoc] in 1947 and had retained 50 percent of its original oxytocic potency. Homogeneous oxytocin exhib- iting a high level of biological activity was isolates! from this material by the Craig countercurrent technique. The amino acid composition of an acid hydrolysate of this material, de- termined by the Moore-Stein technique, showed the presence of cystine, glutamic acid, aspartic acid, glycine, isoleucine, leucine, praline, and tyrosine in molar ratios of Id. In ad- dition to these amino acid residues, the hydrolysate con- tained three moles of ammonia. The amino acid residues plus ammonia accounted for 97 percent of the hydrolyzed

556 BIOGRAPHICAL MEMOIRS material. Molecular weight determinations were in agree- ment with a monomer. Oxytocin was oxicTized with performic acid, and the amino acic! composition of the oxidizer! material was cletermined. The composition was identical to that of the unoxidized material, except that in lieu of cystine two mole- cules of cysteic acid were present. It follower! from this and other results that oxytocin was a cyclic peptide. Using the dinitrofluorobenzene technique of Sanger, it was shown that oxytocin contained a free amino group that was derived from one of the two cysteine residues; a free carboxy} group was not present. By a combination of the Edman technique and analysis of partial acid hydroly- sates, the amino acid sequence of oxytocin was established as H-Cys-Tyr-Ile-Glu-Asp-Cys-Pro-Leu-Gly-OH. The final, as yet unanswered, question relatecI to the sources of the three ammonia molecules. These were shown to be asparagine, glutamine, and glycinamide. Thus the structure of oxytocin was establishe(1 as H-Cys-Tyr-~le-GIn-Asn-Cys-Pro-Leu-Gly- NH2. In his characteristically cautious approach, do Vig- neauc] commented as follows: "It is obvious that, in spite of the fact that this was the only structure we could arrive at through the realization of the results from our clegradative work, synthetic proof of structure was mandatory." The crucial steps in du Vigneaud's oxytocin synthesis were basest on reactions in liquid ammonia he had investigated many years earlier. When subjected to reduction with sodium in liquic] ammonia, oxytocin was converted to the open-chain oxytoceine, and this on air oxidation reconstituted biologi- cally active oxytocin. This behavior of oxytocin was the key for its successful synthesis. Another mocle} study, using the natural hormone, was performed that suggested the strategy for a successful synthesis. Oxytocin was reducecl to the open- chain oxytoceine, and benzy] chloride was a(l(le(1 to the re- action mixture, adorning S,S'-ctibenzyloxytoceine. Deben

VINCENT DU VIGNEAUD 557 zylation of this material with sodium in liquid ammonia followed by air oxidation regenerated biologically active ox- ytocin. The facile ring closure to the 20-membered ring structure of oxytocin from the open-chain pepti(le oxytoceine in(li- cated that the open-chain structure had a preferred confor- mation in which the two SH groups are located in close prox- imity for cyclization to occur. This appears to constitute the first example of the now well-established principle that the amino acid sequence of a protein endows it with the ther- moclynamic information necessary for folding into a specific conformation. Based on these moclel reactions, flu Vigneaud synthesized N-benzyloxycarbonyI-S,S'-clibenzyloxytoceine and converted the synthetic material into active oxytocin in the manner discussed above. The synthetic oxytocin was iclentical with the natural hormone. The first oxytocin syn- thesis was communicated to the Journal of the American Chem- ical Society on July 13, 1953. The paper concluded with the following statement: If the synthetic product truly represents oxytocin, which it does so far as we are concerned, this would constitute the first synthesis of a polypep- tide hormone. What effect slight changes in the structure of a compound of such complexity might have on chemical, physical, and biological prop- erties must be investigated. While the work on oxytocin was uncler way, the structure of vasopressin was also determined. With a wealth of data based on degradation studies, paralleling those outlinecl for oxytocin, a structure for arginine vasopressin was arrived at that was very similar to that of oxytocin. This hormone em- boclies the same ring structure as oxytocin but contains two amino acid exchanges. Isoleucine is replacecI by phenylala- nine and leucine is substituted by arginine. Lysine vasopres- sin contains lysine in lieu of arginine.

558 BIOGRAPHICAL MEMOIRS A synthesis of lysine vasopressin was completect in 1960. The observation by du Vigneaud that certain combinations of amino acids into pepticles can result in compounds exhib- iting potent physiological activities opened a vast field of bio- logical and chemical research. He stated, "It is a little startling to think that the amino acids when put together in a certain way, in a particular architecture, can react to such an array of compounds exhibiting such a variety of physiological and pharmacological properties." D u Vi gneaud 's fin ctin gs with oxytocin and vaso pressin were of great funciamental importance: They demonstrated for the first time that replacement of certain amino acid res- idues in the sequence of a physiologically active peptide can bring about significant changes in biological action. The ex- change in oxytocin of isoleucine for phenylalanine and of leucine for arginine (or lysine) alters the physiological activity of the molecule from one of mainly oxytocic to one with mainly vasopressor potency. These discoveries have stimu- latecI much research into the relations between peptide struc- ture and physiological function. Hundreds of analogs of the posterior pituitary hormones have been prepared as a con- sequence of (lu Vigneau(l's work, anti his pioneering studies have spawned the recent explosive activity in the pepticle fielct. Thus far we have been concerned with the story of du Vigneaud's life and with his many scientific accomplishments. We may now ask: Who was this man and what was the at- mosphere in his laboratory that promoted such a wealth of funciamental work? His laboratory was extremely well orga- nized. Since he was a very busy man who was not always available for consultations, he initiated a system of colored slips for communicating with him. There was a pink slip for suggesting new ideas and new research approaches, there

VINCENT DU VIGNEAUD 559 was a green slip for reporting research results, and, finally, a white slip for requesting microanalytical services. The "greens" were flu Vigneaud's favorite. He wanted them at least weekly from every researcher in the group, anc! he read them with extreme care. To those who were reluctant to write up half-finished experiments, he insisted that that was the fun of the research to him. He couIcin't remember (he said) the results presented to him in a neat package at the end nearly as well as if he hac! been in on them as they cleveloped day by (lay. Many a collaborator was awe(1 by his memory for details in someone else's research reports, from months or years gone by, which he could bring to bear on the problem at hancI. The potential sect thus available, once appreciated, li(1 a lot to lighten the task of grinding out the green slips! But, besicles all of this red tape, there was ample opportunity to have a private audience with the chief. The laboratory was a busy place incleecI, and hard work was the order of the clay. Graduate students were expecter! to spenct several evenings a week in the laboratory, as well as part of Saturday, and papers were frequently written late into the night. Professor clu Vigneaucl lived in the suburbs of New York, but he maintainec! a beautifully furnished room in the department where he spent many a night cluring the week. These were the evenings when he came to visit with his collaborators. Smoking a White Owl cigar, which he grace- fully waved poised between his strong fingers, he sharer! a cold soft drink with us and discussed the latest research re- sults. Speaking quietly and easily, he used such words as "ex- citing," "surprising," "intriguing"-all suggesting great plea- sure in the stepwise evolution of the research. He was always highly interested in the clay's results and was truly devoted to his scientific work. He felt very secure and loved his work. To a reporter he said:

560 BIOGRAPHICAL MEMOIRS I have had the privilege and the thrill of following those researches that I've always wanted to do. I've always had the privilege of working on what I've wanted to work on. I have been accompanied in the various stages of these exploratory researches by a group of hne and loyal asso- ciates. I've also been fortunate throughout the years in the generous re- search support I've received from various sources. He had a highly critical attitude toward laboratory results and this permeates his writings. Every possible angle of a project was discussed at great length, and new approaches anti ideas that could clarify an issue were explorer! in depth. Papers were written in collaboration with those who dicT the work; a secretary was present, and while discussions went on she was typing the latest version of a ciraft. A great many versions were hammered out before the chief was satisfied. Unquestionably, du Vigneaud was in command, and he was highly respected by his collaborators. He hacT a jovial manner with people, anct every year he invited his entire crew to his home in Scarsciale for a picnic with softball and other entertainment. "Dee," as he was known by his colleagues over the years, associated with a great number of graduate stu- dents, postdoctoral fellows, and visiting professors. All the people who ever worked in Dee's laboratory belonged auto- matically to the V clu V Club. He kept in constant touch with us, and every year cluring the Federation meetings we all got together for beer anct pretzels to share time with former col- leagues, the chief, and his charming wife, ZelIa. THE AUTHOR IS INDEBTED to Drs. Martha Ferger, Sofia Sim- monds, and Marilyn Renee Brown for their help in collecting source materials. A number of the quotations are taken from an interview published in the journal of Chemical Education, 53~19761: 8-12.

VINCENT DU VIGNEAUD HONORS AND DISTINCTIONS D E G R E E S B.S., University of Illinois, 1923 M.S., University of Illinois, 1924 Ph.D. (Biochemistry), University of Rochester, 1927 HONORARY DEGREES D.Sc., New York University, 1955 D.Sc., Yale University, 1955 D.Sc., University of Illinois, 1960 D.Sc., University of Rochester and St. Louis University, 1965 UNIVERSITY APPOINTMENTS 561 National Research Council Fellow, Johns Hopkins University, 1927-28 National Research Council Fellow, Kaiser Wilhelm Institute, Dres- den, Germany, and University of Edinburgh Medical School, 1928-29 Associate, University of Illinois, 1927-30 Professor and Head of Department of Biochemistry, School of Medicine, George Washington University, 1932-38 Professor and Head of Department of Biochemistry, Cornell Uni- versity Medical College, 1938-64 Professor Emeritus of Chemistry, Department of Chemistry, Cor- nell University, 1964-74. MEMBERSHIPS National Academy of Sciences, 1944 American Philosophical Society, 1944 Royal Society of Sciences of Uppsala, Honorary Fellow of the Royal Society of Edinburgh, 1954 Honorary Fellow, Royal Institute of London, 1959 AWARDS AND LECTURESHIPS 1950 Hillebrand Award, Washington Chemical Society, 1936 Foster Lecturer, University of Buffalo, 1939 Harvey Society Lecturer, 1942

562 BIOGRAPHICAL MEMOIRS Meade-Johnson Vitamin B Complex Award, American Institute of Nutrition, 1942 Hitchcock Lecturer, University of California, 1944 Nichols Medal, New York Section, American Chemical Society, 1945 Borden Award, Association of American Medical Colleges, 1947 Visiting Lecturer, American Swiss Foundation for Scientific Ex change, Switzerland, 1947 Award of Merit for War Research, United States Government, 1948 Lasker Award, American Public Health Association, 1948 Stieglitz Memorial Lecturer, University of Chicago, 1948 Eastman Lecturer, University of Rochester, 1949 Liversidge Lecturer, University of Cambridge, 1949 Special Lecturer, University of London, 1949 Messenger Lecturer, Cornell University, 1950 Herter Lecturer, New York University, 1952 Fdsel B. Ford Lecture, Henry Ford Hospital, 1954 Goldforb Lecturer, 1954 Harvey Society Lecturer, 1954 Osborne and Mendel Award, 1954 John Scott Award, Philadelphia, 1954 Remsen Memorial Lecturer, Johns Hopkins University, 1954 Scientific Award, American Pharmaceutical Manufacturers' Asso ciation, 1954 Chandler Award, Columbia University, 1955 Annual Hanna Lecturer, Western Reserve University, 1955 Nobel Prize in Chemistry, Nobel Foundation, 1955 Passano Award, Passano Foundation, 1955 Dakin Memorial Lecturer, Adelphi College, 1956 Willard Gibbs Medal, Chicago Section, American Chemical Society, 1956 Nieuwland Lecturer, University of Notre Dame, 1956 Edgar Fahs Smith Lecturer, University of Pennsylvania, 1958 Alumni Achievement Award, University of Illinois, 1959 Martland Memorial Lecturer, 1959 Nutrition Foundation's 20th Anniversary Award, 1961 Pirquet Society of Clinical Medicine Medalist, 1964 American College of Physicians Award, 1965 The Eli Lilly Lecture Award, Endocrine Society, 1967

VINCENT DU VIGNEAUD BIBLIOGRAPHY 1924 563 With C. S. Marvel. Pressor anesthetics. l. Am. Chem. Soc., 46: 2093-99. With C. S. Marvel. A new organic reagent for the detection of ni- trates and perchlorates. I. Am. Chem. Soc., 46:2661-63. 1925 With Walter G. Karr. Carbohydrate utilization. I. Rate of disap- pearance of d-glucose from the blood. }. Biol. Chem., 66:281- 300. 1927 The labile sulfur of insulin. Proc. Soc. Exp. Biol. Med., 24:547-48. Some useful modifications of the haldane gas-analysis apparatus. }. Lab. Clin. Med., 13:175-84. Is insulin inactivated by glucose? l. Biol. Chem., 73:275. The sulfur of insulin. l. Biol. Chem., 75:393 - 405. 1928 With H. Jensen and Oskar Wintersteiner. Studies on crystalline insulin. III. Further observations on the crystallization of in- sulin and on the nature of the sulfur linkage. The isolation of cystine and tyrosine from hydrolyzed crystalline insulin. J. Pharmacol. Exp. Ther., 32:367-85. With H. Jensen and Oskar Wintersteiner. Studies on crystalline insulin. IV. The isolation of arginine, histidine and leucine. i. Pharmacol. Exp. Ther., 32:387-95. With Oskar Wintersteiner and H. Jensen. Studies on crystalline insulin. V. The distribution of nitrogen in crystalline insulin. I. Pharmacol. Exp. Ther., 32: 397-411. With E. M. K. Gelling and C. A. Eddy. Studies on crystalline insu- lin. VI. Further contributions to the question whether or not crystalline insulin is an adsorption product. }. Pharmacol. Exp. Ther., 33:497-509. 1929 With Max Bergmann and Leonidas Zervas. Synthese arginin- haltiger peptide: d-Tyrosyl-d-arginin und sein anhydrid. Ber. Dtsch. Chem. Ges., 62:1905-9.

564 BIOGRAPHICAL MEMOIRS With Max Bergmann and Leonidas Zervas. Acylwanderung und spaltungsvorgange bei acylierten dioxo-piperazinen. Ber. Dtsch. Chem. Ges., 62:1909-13. 1930 With Leonore Hollandor. The resolution of inactive cystine. Proc. Soc. Exp. Biol. Med., 28:46-47. With L. F. Audrieth and H. S. Loring. The reduction of cystine in liquid ammonia by metallic sodium. l. Am. Chem. Soc., 52:4500-4504. 1931 With Hubert S. Loring. The isolation of two isomeric inactive cys- tines. Proc. Soc. Exp. Biol. Med., 29:41-42. With Alice Fitch, E. Pekarek, and W. W. Lockwood. The inactiva- tion of crystalline insulin by cysteine and glutathione. J. Biol. Chem., 94:233-42. With Leonore Hollander. The resolution of inactive cystine and isolation of pure dextrorotatory cystine. i. Biol. Chem., 94:243-52. 1932 With Curtis E. Meyer. Isolation of methionine by enzymatic hy- drolysis. t. Biol. Chem., 94:641-45. With Robert Ridgely Sealock. The racemization of acety-l- tryptophane. J. Biol. Chem., 96:511-17. W~th curt~s t. Meyer. ~ ne racem~zat~on ot amino acids in aqueous solution by acetic anhydride. J. Biol. Chem., 98:295-308. With Robert Ridgely Sealock and Cecil Van Etten. Availability of d-tryptophane and its acetyl derivative to the animal body. J. Biol. Chem., 98:565 -75. With Ralph Dorfmann and Hubert S. Loring. A comparison of the growth-promoting properties of d- and l-cystine. J. Biol. Chem., 98:577-89. With Curtis E. Meyer. The temporary formation of the azlactone ring in the racemization of acyl derivatives of amino acids with acetic anhydride. i. Biol. Chem., 99:143-51. With Lewis W. Butz. The formation of a homologue of cystine by the decomposition of methionine with sulfuric acid. t. Biol. Chem., 99:135-42. . . . _ . . ~

VINCENT DU VIGNEAUD 1933 565 With Helen M. Dyer and J. Harmon. The growth-promoting prop- erties of homocystine when added to a cystine-deficient diet and proof of structure of homocystine. l. Biol. Chem., 101 :719-26. With Hubert S. Loring. The isolation and characterization of me- socystine. l. Biol. Chem., 102: 287-95. With Robert H. Sifferd and Robert R. Sealock. The heat precipi- tation of insulin. I. Biol. Chem., 102:521-33. With Hubert S. Loring and Ralph Dorfmann. The availability of mesocystine for promotion of growth in connection with cys- tine-deficient diets. I. Biol. Chem., 103:399-403. 1934 With Harold A. Craft and Hubert S. Loring. The oxidation of the stereoisomers of cystine in the animal body. I. Biol. Chem., 104:81-89. Insulin and diabetes. Sci. Mon., 38:565-68. With Hubert S. Loring and Harold A. Craft. The oxidation of the sulfur of homocystine, methionine and S-methylcysteine in the animal body. I. Biol. Chem., 105:481-88. With Helen M. Dyer, Chase B. Jones, and Wilbur I. Patterson. The synthesis of pentocystine and homomethionine. {. Biol. Chem., 106:401-7. With Hubert S. Loring. The solubility of the stereoisomers of cys- tine with a note on the identity of stone and hair cystine. i. Biol. Chem., 107: 267-74. With Hubert S. Loring and Harold A. Craft. The oxidation of the sulfur of the acetyl and formyl derivatives of d- and l-cystine in the animal body. }. Biol. Chem., 107:519 -25. With Robert H. Sifferd. Oxidation of cystine sulfur to sulfate by ferric chloride. Proc. Soc. Exp. Biol. Med., 32:332-33. 1935 With Helen M. Dyer. A study of the physiological availability of pentocystine and homomethionine. i. Biol. Chem., 108:73 -78. The chemistry of hormones from a structural standpoint. Sci. Mon., 40:138-45. With Robert H. Sifferd. A new synthesis of carnosine, with some observations on the splitting of the benzyl group from carbo

566 BIOGRAPHICAL MEMOIRS benzoxy derivatives and from benzylthio ethers. i. Biol. Chem., 108:753-61. With Wilbur I. Patterson. The preparation of the optically active isomers of homocystine and the demonstration of their config- urational relationship to naturally occurring methionine. i. Biol. Chem., 109:97-103. With Helen M. Dyer. A study of the availability of d- and l- homocystine for growth purposes. I. Biol. Chem., 109:477-80. With Robert Ridgely Sealock. Studies on the reduction of pitressin and pitocin with cysteine. I. Pharmacol. Exp. Ther., 54:433-47. With Hubert S. Loring. The synthesis of crystalline cystinyldigly- cine and benzylcysteinylglycine and their isolation from gluta- thione. J. Biol. Chem., 111:385-92. With Wilbur I. Patterson. The synthesis of homocystine. I. Biol. Chem., 111 :393-98. With Byron Riegel. The isolation of homocysteine and its conver- sion to a thiolactone. I Biol. Chem., 112: 149-54. With Robert H. Sifferd and Gail Miller. On the absence of thiol- histidine in insulin. Proc. Soc. Exp. Biol. Med., 33:371-73. 1936 With Robert Ridgely Sealock and Cecil Van Etten. The question of the utilization of tryptophane administered subcutaneously. i. Biol. Chem., 112:451-56. With Helen M. Dyer. The chemistry and metabolism of compounds of sulfur. Annul Rev. Biochem., 5: 159-80. With Wilbur I. Patterson. The synthesis of djenkolic acid. i. Biol. Chem., 114:533-38. With Madison Hunt. The synthesis of d-carnosine, the enanti- morph of the naturally occurring form, and a study of its de- pressor effect on the blood pressure. I. Biol. Chem., 115:93- 100. With Helen M. Dyer. The utilization of glutathione in connection with a cystine-deficient diet. J. Biol. Chem., 115:543 -49. With Wilbur I. Patterson and Helen M. Dyer. The synthesis of Di- N-methylhomocystine and N-methylmethionine and a study of their growth-promoting ability in connection with a cystine- deficient diet. i. Biol. Chem., 1 1 6: 277-84. With Gail Lorenz Miller. A synthesis of glutathione. J. Biol. Chem., 116:469-76.

VINCENT DU VIGNEAUD 1937 567 With Otto K. Behrens. A method for protecting the imidazole ring of histidine during certain reactions and its application to the preparation of l-amino-N-methylhistidine. l. Biol. Chem., 117:27-36. The cancer symposium of the medical sciences section. Science, 84:439-40. With Robert H. Sifferd and George W. Irving, in The utilization of l-carnosine by animals on a histidine-deficient diet. }. Biol. Chem., 117:589 -97. With Gail Lorenz Miller. The cystine content of insulin. I. Biol. Chem., 118: 101-10. With Hubert S. Loring and Gail Lorenz Miller. The synthesis of cx-glutamylcysteinylglycine (isoglutathione). J. Biol. Chem., 118:391-95. With Helen M. Dyer. The chemistry and metabolism of the com- pounds of sulfur. Annul Rev. Biochem., 6:193-210. With Helen M. Dyer and Chase Breese Jones. Studies of the phys- iological behavior of the acetyl derivatives of the optical isomers of homocystine; a biological proof of their stereostructure. - Biol. Chem., 119:47-57. Some aspects of the study of insulin. I. Wash. Acad. Sci., 27:365. With Chase Breese Jones. The synthesis of hexocystine and hexo- methionine and a study of their physiological availability. J. Biol. Chem., 120:11-20. With Otto K. Behrens. The synthesis of anserine from 1- 1- methylhistidine. I. Biol. Chem., 120:517-22. With William T. McClosky, Lloyd C. Miller, and Madison Hunt. On the alleged oxytocic activity of l-carnosine. Proc. Soc. Exp. Biol. Med., 37:60-61. J 1938 With Oliver I. Irish. The role of the acetyl derivative as an inter- mediary stage in the biological synthesis of amino acids from keto acids. I. Biol. Chem., 122:349-70. With George W. Irving, Jr., Helen M. Dyer, and Robert Ridgely Sealock. Electrophoresis of posterior pituitary gland prepara- tions. I. Biol. Chem., 123:45-55. With Wilbur I. Patterson. The synthesis of tetradeuterohomocys- tine and dideuteromethionine. I. Biol. Chem., 123:327-34.

568 BIOGRAPHICAL MEMOIRS With George W. Irving, in The differential migration of the pres- sor and oxytocic hormones in electrophoretic studies of the un- treated pressjuice of the posterior lobe of the pituitary gland. }. Biol. Chem., 123 :485 - 89. With Madison Hunt. The preparation of d-alanyl-l-histidine and 1- alanyl-l-histidine and an investigation of their effect on the blood pressure in comparison with l-carnosine. i. Biol. Chem., 124:699-709. A brief review of studies on homocystine. Nucleus, January. With Madison Hunt. A preliminary study of Q-I-aspartyl-l-histidine as a possible precursor of l-carnosine. i. Biol. Chem., 125:269- 74. With Wilbur I. Patterson and Madison Hunt. Opening of the ring of the thiolactone of homocysteine. i. Biol. Chem., 126:217-31. The role which insulin has played in our concept of protein hor- mones, and a consideration of certain phases of the chemistry of insulin. Cold Spring Harbor Symp. Quant. Biol., 6:275-85. Earl Baldwin McKinley. Science, 88:344-45. 1939 With Madison Hunt. The synthesis of the next higher and lower homologues of l-carnosine: ~y-Aminobutyryl-l-histidine and glycyl-l-histidine. J. Biol. Chem., 127:43-48. With Otto K. Behrens. Carnosine and anserine. Ergebnisse der Physiol. Biol. Chem. Exp. Pharmakol., 41:917. With Madison Hunt. A further contribution on the relationship of the structure of l-carnosine to its depressor activity. }. Biol. Chem., 127:727-35. With Marian Wood Kies, Helen M. Dyer, and John L. Wood. A study of the utilization of the optical isomers of N,N'-Di- methylcystine. }. Biol. Chem., 128:207-16. With Joseph P. Chandler, A. W. Moyer, and Dorothy M. Keppel. The ability of homocystine plus choline to support growth of the white rat on a methionine-free diet. i. Biol. Chem.,128:cviii. With John L. Wood and Oliver J. Irish. The optical inversion of the benzyl derivatives of d-cysteine and d-homocysteine in viva. }. Biol. Chem., 129:171-77. With John L. Wood. Racemization of benzyl-l-cysteine, with a new method of preparing d-cystine. J. Biol. Chem., 130: 109 -14.

VINCENT DU VIGNEAUD 569 With Helen M. Dyer and Marian Wood Kies. A relationship be- tween the nature of the vitamin B complex supplement and the ability of homocystine to replace methionine in the diet. }. Biol. Chem., 130:325-40. With Joseph P. Chandler, A. W. Moyer, and Dorothy M. Keppel. The effect of choline on the ability of homocystine to replace methionine in the diet. T. Biol. Chem., 131:57-76. With John L. Wood. A new synthesis of cystine. }. Biol. Chem., 131 :267-71. With Mildred Cohn, George Bosworth Brown, Oliver J. Irish, Ru- dolph Schoenheimer, and D. Rittenberg. A study of the inver- sion of d-phenylaminobutyric acid and the acetylation of 1- phenyl-aminobutyric acid by means of the isotopes of nitrogen and hydrogen. }. Biol. Chem., 131:273-96. With Gail Lorenz Miller and Clement i. Rodden. On the question of the presence of methionine in insulin. I. Biol. Chem., 131:631-40. 1940 With Paul Gyorgy, Donald B. Melville, and Dean Burk. The pos- sible identity of vitamin H with biotin and coenzyme R. Science. 91 :243-45 With John L. Wood. On the synthesis of serine. i. Biol. Chem., 134:413-16. With George W. Irving, Jr. A simple laboratory method for obtain- ing preparations containing presser and oxytocic activity from the posterior lobe of the pituitary gland. I. Am. Chem. Soc., 62:2080-82. With Joseph P. Chandler. The comparative action of choline and betaine in effecting the replacement of methionine by homo- cystine in the diet. I. Biol. Chem., 135:223-29. With Joseph P. Chandler, Mildred Cohn, and George Bosworth Brown. The transfer of the methyl group from methionine to choline and creatine. }. Biol. Chem., 134:787-88. With Donald B. Melville, Paul Gyorgy, and Catherine S. Rose. On the identity of vitamin H with biotin. Science, 92:62-63. With Paul Gyorgy, Catherine S. Rose, Klaus Hofmann, and Donald B. Melville. A further note on the identity of vitamin H with biotin. Science, 92:609.

570 BIOGRAPHICAL MEMOIRS 1941 With Mildred Cohn and George W. Irving, Jr. The amphoteric nature of the presser principle of the posterior lobe of the pi- tuitary gland. {. Biol. Chem., 137:635-42. With George Bosworth Brown. The synthesis of S-~3-amino-13- carboxyethyl)-homocysteine. T. Biol. Chem., 137:611-15. With George W. Irving, Jr., and Helen M. Dyer. Purification of the presser principle of the posterior lobe of the pituitary gland by electrophoresis. l. Am. Chem. Soc., 63:503-6. With John L. Wood and Francis Binkley. Acetylation in vivo of p- bromophenyl-d-cysteine. I. Biol. Chem., 138: 369-74. . . With George Bosworth Brown. The synthesis of the new sulfur- containing amino acid (lanthionine) isolated from sodium- carbonate treated wool. l. Biol. Chem., 138:151-54. With Joseph P. Chandler and A. W. Moyer. The inability of creatine and creatinine to enter into transmethylation in viva. i. Biol. Chem., 139:917-23. With Dean Burk and Richard I. Winzler. The role of biotin in fer- mentation and the Pasteur eEect. I. Biol. Chem., 140:xxi-xxii. With Gail Lorenz Miller and Otto K. Behrens. A synthesis of the aspartic acid analogue of glutathion (asparthione). J. Biol. Chem., 140:411-16. With Mildred Cohn, Joseph P. Chandler, lay R. Schenck, and Sofia Simmonds. The utilization of the methyl group of methionine in the biological synthesis of choline and creatine. I. Biol. Chem., 140:625-41. With Klaus Hofmann, Donald B. Melville, and Paul Gyorgy. Iso- lation of biotin (vitamin H) from liver. l. Biol. Chem., 140:643- 51. With George Bosworth Brown. The stereoisomeric forms of lan- thionine. I. Biol. Chem., 1 40: 767-7 1 . With Klaus Hofmann, Donald B. Melville, and Julian R. Rachele. The preparation of free crystalline biotin. J Biol. Chem., 140:763 -66. With George Bosworth Brown. The effect of certain reagents on the activity of biotin. J Biol. Chem., 141: 85-89. With Klaus Hofmann and Donald B. Melville. Characterization of the functional groups of biotin. I. Biol. Chem., 1 4 1: 207-1 4. . .

VINCENT DU VIGNEAUD 571 With Donald B. Melville and Klaus Hofmann. Resynthesis of biotin from a degradation product. Science, 94:308-9. Interrelationships between choline and other methylated com- pounds. Biol. Symp., 5:234-47. With George Bosworth Brown and Roy W. Bonsnes. The formation of lanthionine on treatment of insulin with dilute alkali. i. Biol. Chem., 141:707-8. With Klaus Hofmann and Donald B. Melville. Formation of adipic acid by oxidative degradation of diaminocarboxylic acid de- rived from biotin. J. Am. Chem. Soc., 63:3237-38. 1942 Biotin. In: BiologacalAction ofthe Vitamins, p. 44. Chicago: University of Chicago Press. With Donald B. Melville, Klaus Hofmann, and Eleanor Hague. The isolation of biotin from milk. I. Biol. Chem., 142:615-18. With Klaus Hofmann and Donald B. Melville. On the structure of biotin. }. Am. Chem. Soc., 64:188-89. With George Bosworth Brown and Joseph P. Chandler. The syn- thesis of 11-S-(,B-amino-~-carboxyethyl)-homocysteine and the replacement by it of cystine in the diet. I. Biol. Chem., 143:59- 64. With A. W. Moyer. The structural specificity of choline and betaine in transmethylation. }. Biol. Chem., 143:373-82. With Juliet Spangler, Dean Burk, Charles Kensler, K. Sugiura, and C. P. Roads. The procarcinogenic effect of biotin in butter yel- low tumor formation. Science, 95: 174-76. With Francis Binkley and William P. Anslow, fir. The formation of cysteine from Il-S(~-amino-~-carboxyethyl)-homocysteine by liver tissue. I. Biol. Chem., 143:559-60. With Klaus Hofmann and Donald B. Melville. Adipic acid as an oxidation product of diaminocarboxylic acid derived from bio- tin. I. Biol. Chem., 1 44:5 1 3 -1 8. With Francis Binkley. The formation of cysteine from homocys- teine and serine by liver tissue of rats. l. Biol. Chem., 144:507- 11. The relationship of the chemist to medicine. }. Am. Med. Assoc., 119:207-8.

572 BIOGRAPHICAL MEMOIRS With Karl Dittmer, Klaus Hofmann, and Donald B. Melville. Yeast- growth-promoting effect of diaminocarboxylic acid derived from biotin. Proc. Soc. Exp. Biol. Med., 50:374-75. With Donald B. Melville and Klaus Hofmann. The hydrolysis of biotin sulfone. i. Biol. Chem., 145: 101-5. With Karl Dittmer, Eleanor Hague, and Barbara Long. The growth-stimulating effect of biotin for the diptheria bacillus in the absence of pimelic acid. Science, 96: 186-87. With Glen W. Kilmer, Marvin D. Armstrong, and George Bosworth Brown. Synthesis of a 3,4-diaminotetrahydrothiophene and a comparison of its stability with the diaminocarboxylic acid de- rived from biotin. l. Biol. Chem., 145:495-501. With Klaus Hofmann, Glen W. Kilmer, Donald B. Melville, and Hugh H. Darby. The condensation of phenanthraquinone with the diaminocarboxylic acid derived from biotin. I. Biol. Chem., 145:503-9. With Donald B. Melville, Karl Folkers, Donald E. Wolf, Ralph Moz- ingo, John C. Keresztesy, and Stanton A. Harris. The structure of biotin: A study of desthiobiotin. i. Biol. Chem., 146:475-85. With Donald B. Melville, A. W. Moyer, and Klaus Hofmann. The structure of biotin: The formation of thiophenevaleric acid from biotin. i. Biol. Chem., 146:487-92. The structure of biotin. Science, 96:455-61. With Sofia Simmonds. Transmethylation as a metabolic process in man. }. Biol. Chem., 146:685-86. The significance of the labile methyl groups in the diet and their relation to transmethylation. Harvey Lect., 38: 39- 62. 1943 With George W. Irving, Jr. Hormones of the posterior lobe of the pituitary gland. Ann. N.Y. Acad. Sci., 43:273-307. With Jay R. Schenck, Sofia Simmonds, Mildred Cohn, and Carl M. Stevens. The relation of transmethylation to anserine. I. Biol. Chem., 149:355 -59. With Sofia Simmonds, Mildred Cohn, and Joseph P. Chandler. The utilization of the methyl groups of choline in the biological syn- thesis of methionine. i. Biol. Chem., 149:519-25. With Donald B. Melville, Karl Dittmer, and George Bosworth Brown. Desthiobiotin. Science, 98:497-99.

VINCENT DU VIGNEAUD 573 With C. }. Kensler, C. Wadsworth, K. Sugiura, C. P. Rhoads, and Karl Dittmer. The influence of egg white and avidin feeding on tumor growth. Cancer Res., 3:823-24. 1944 With Francis Binkley and John L. Wood. A study of the acetylation in viva of certain d-amino acids. }. Biol. Chem., 153:495-500. With Karl Dittmer and Donald Melville. The possible synthesis of biotin from desthiobiotin by yeast and the antibiotic effect of desthiobiotin for L. casei. Science, 99:203 -5. With lay R. Schenck. A study of the synthesis of p-alanine in the white rat. l. Biol. Chem., 153:501-5. With Karl Dittmer, Paul Gyorgy, and Catharine S. Rose. A study of biotin sulfone. Arch. Biochem., 4:229-42. With Glen W. Kilmer. A synthesis of methionine containing isotopic carbon and sulfur. }. Biol. Chem., 154:247-53. With Richard }. Winzler and Dean Burk. Biotin in fermentation, respiration, growth and nitrogen assimilation by yeast. Arch. Biochem., 5:25-47. With Karl Dittmer. Antibiotins. Science, 100: 129-31. With Glen W. Kilmer, Julian R. Rachele, and Mildred Cohn. On the mechanism of the conversion in vivo of methionine to cys- tine. }. Biol. Chem., 155 :645-51. 1945 With John L. Wood. The synthesis of optically inactive desthiobi- otin. l. Am. Chem. Soc., 67:210-12. The relationship of structure to biotin and antibiotin activity. (Nichols Medal Lecture). Chem. Eng. News., 23:623-25. With Herbert McKennis, Jr., Sofia Simmonds, Karl Dittmer, and George Bosworth Brown. The inhibitions of the growth of yeast by thienylalanine. }. Biol. Chem., 159:385-94. With Sachchidananda Banerjee and Karl Dittn~er. A microbiolog- ical and fluorometric test for minute amounts of alloxan. Sci- ence, 101 :647 - 49. With Sofia Simmonds. A further study of the lability of the methyl group of creatine. Proc. Soc. Exp. Biol. Med., 59:293-94. With Sofia Simmonds, Joseph P. Chandler, and Mildred Cohn. Syn- thesis of labile methyl groups in the white rat. i. Biol. Chem., 159:755-56.

574 BIOGRAPHICAL MEMOIRS Protein chemistry and medicine. Science, 102:24-25. The role of methionine in the metabolism of the body. In: "The Doctors Talk it Over" Series, November 27, 1945. 1946 With Mildred Cohn, Sofia Simmonds, and Joseph P. Chandler. The effect of the dietary level of methionine on the rate of trans- methylation reactions in viva. }. Biol. Chem., 162:343 -51. Scientific contributions of the medalist Wendell M. Stanley Nich- ols Medal Award, 1946. Chem. Eng. News, 24:752-55. With Herbert McKennis, fir. The synthesis of homodesthiobiotin and related compounds. }. Am. Chem. Soc., 68:832-35. With George Bosworth Brown. The thiourea analogue of desthio- biotin. }. Biol. Chem., 163:761-66. With Karl Dittmer and Martha F. Ferger. Synthesis of imidazoli- done aliphatic acids. I. Biol. Chem., 164: 19-28. With Joseph P. Chandler, Sofia Simmonds, A. W. Moyer, and Mildred Cohn. The role of dimethyl- and monomethylamino- ethanol in transmethylation reactions in viva. }. Biol. Chem., 164:603 -13. With Karl Dittmer, Glenn Ellis, and Herbert McKennis, fir. The effect of amino acids on the microbial growth inhibition pro- duced by thienylalanine. I. Biol. Chem., 164:761-71. With John L. Wood. A note on the conversion in vivo of the S- benzyl-N-methyl derivatives of cysteine and homocysteine to the N-acetyl-S-benzyl derivatives of cysteine and homocysteine. I. Biol. Chem., 165:95-96. With Sofia Simmonds, Joseph P. Chandler, and Mildred Cohn. A further investigation of the role of betaine in transmethylation reactions in vivo. l. Biol. Chem., 165:639-48. With Frederick H. Carpenter, Robert W. Holley, Arthur H. Liver- more, and Julian R. Rachele. Synthetic penicillin. Science, 104:431-33. With Sofia Simmonds and Mildred Cohn. A further investigation of the ability of sarcosine to serve as a labile methyl donor. I. Biol. Chem., 166 :47-52. With William P. Anslow, Jr., and Sofia Simmonds. The synthesis of the isomers of cystathionine and a study of their availability in sulfur metabolism. J. Biol. Chem., 166:35 -45.

VINCENT DU VIGNEAUD 1947 575 With Marvin D. Armstrong. A new synthesis of djenkolic acid. }. Biol. Chem., 168:373-77. With Lyman C. Craig, George H. Hogeboom, and Frederick H. Carpenter. Separation and characterization of some penicillins by the method of counter-current distribution. I. Biol. Chem., 168:665-86. With Karl H. Dittmer. Antibiotin activity of imidazolidone aliphatic acids. I. Biol. Chem., 169:63-70. With Cosmo G. Mackenzie, Joseph P. Chandler, Elizabeth B. Keller, Julian R. Rachele, Nancy Cross, and Donald B. Melville. The demonstration of the oxidation in vivo of the methyl group of methionine. I. Biol. Chem., 169:757-58. With William P. Anslow, [r. The cleavage of the stereoisomers of cystathionine by liver extract. }. Biol. Chem., 170:245-50. With Sofia Simmonds and Mildred Cohn. A study on transmeth- ylation with methionine containing varying amounts of deuter- ium in the methyl group. J. Biol. Chem., 170:631-33. With Carl M. Stevens. Preparation of highly purified mustard gas and its action on yeast. }. Am. Chem. Soc., 69:1808-9. With Joseph P. Chandler, Martha W. Gerrard, and W. M. Stanley. The utilization for animal growth of tobacco mosaic virus as a sole source of protein in the diet. }. Biol. Chem., 171:823-28. 1948 With Cosmo G. Mackenzie. The source of urea carbon. }. Biol. Chem., 172:353-54. With Elizabeth B. Keller and John L. Wood. An investigation of transmethylation from N'-methylnicotinamide. Proc. Soc. Exp. Biol. Med., 67: 182-84. With Marvin D. Armstrong. Mercaptals and mercaptoles of cys- teine. J. Biol. Chem., 173:749-51. With Cosmo G. Mackenzie, Julian R. Rachele, Nancy Cross, and Joseph P. Chandler. Study of the oxidation of the labile methyl group of dietary methionine traced with Ci4. Fed. Proc. Fed. Am. Soc. Exp. Biol., 7~1~:170. With Martha F. Ferger. The microbial growth inhibition produced by optical isomers of Q-2-thienylalanine. J. Biol. Chem., 174:241-46.

576 BIOGRAPHICAL MEMOIRS With George A. Maw. Dimethyl-~-propiothetin, a new methyl do- nor. l. Biol. Chem., 174:381-82. An illustration of the power of isotopes in a biochemical problem. U.S. Nav. Med. Bull., 48, Suppl. 176. With John Eric Wilson. L-penicillamine as a metabolic antagonist. Science, 107:653. With A. W. Moyer and Joseph P. Chandler. Dimethylthetin as a biological methyl donor. i. Biol. Chem., 174 :477-80. With Carl M. Stevens, Harold F. McDuffie, Jr., John L. Wood, and Herbert McKennis, Jr. Reactions of mustard-type vesicants with alpha-amino acids. }. Am. Chem. Soc., 70:1620-24. With Robert Holley, Frederick H. Carpenter, and Arthur H. Liv- ermore. A synthesis of benzylpenillic acid. Science, 108: 136 - 37. With Arthur H. Livermore, Frederick H. Carpenter, and Robert W. Holley. Studies on crystalline D~-benzylpenicillenic acid. J. Biol. Chem., 175:721-26. Migration of the methyl group on the body. Proc. Am. Philos. Soc., 92: 127-35. With John L. Wood, Julian R. Rachele, Carl M. Stevens, and Fred- erick H. Carpenter. The reaction of some radioactive mustard- type vesicants with purified proteins. J. Am. Chem. Soc., 70:2547-50. With Frederick H. Carpenter, John L. Wood, and Carl M. Stevens. Chemical studies on vesicant-treated proteins. }. Am. Chem. Soc., 70:2551-53. With Carl M. Stevens, John L. Wood, and Julian R. Rachele. Studies on acid hydrolysates of vesicant-treated insulin. }. Am. Chem. Soc., 70:2554-56. With Carl M. Stevens and Herbert McKennis, fir. Studies of the effect of mustard-type vesicants on the phenol color reaction of proteins. }. Am. Chem. Soc., 70:2556-59. With Frederick H. Carpenter and Robert A. Turner. Benzylpeni- cillenic acid as an intermediate in the synthesis of benzylpeni- cillin (penicillin G). l. Biol. Chem., 176:893-905. With Gardner W. Stacy and D. Todd. The synthesis of D~-Q,~-di- ethylcysteine and D~-~-ethyl-,B-methylcysteine. J. Biol. Chem., 176:907-14. With Frederick H. Carpenter, Gardney W. Stacy, Dorothy S. Genghof, and Arthur H. Livermore. The preparation and an

VINCENT DU VIGNEAUD 577 tibacterial properties of the crude sodium salts of some syn- thetic penicillins. }. Biol. Chem., 176:915-27. With George A. Maw. An investigation of the biological behavior of the sulfur analogue of choline. }. Biol. Chem., 176: 1029-36. With George A. Maw. Compounds related to dimethylthetin as sources of labile methyl groups. J. Biol. Chem., 176: 1037-45. 1949 With Donald B. Melville. The thiocyanate derivative of benzylpen- icillin methyl ester. In: The Chemistry Penicillin, ed. Hans T. Clarke, John R. Johnson, and Sir Robert Robinson, pp. 269- 309. Princeton: Princeton University Press. With I. L. Wood and M. E. Wright. The condensation of oxazo- lones and d-penicillamine and the resultant antibiotic activity. In: The Chemistry of Penicillin, ed. Hans T. Clarke, John R. John- son, and Sir Robert Robinson, pp. 892-908. Princeton: Prince- ton University Press. With Frederick H. Carpenter. The ~y-lactam of benzylhomopeni- cilloic acid and related compounds. In: The Chemistry of Penicil- lin, ed. Hans T. Clarke, John R. Johnson, and Sir Robert Rob- inson, pp. 1004 - 17. Princeton: Princeton University Press. With Frederick H. Carpenter, Robert W. Holley, Arthur H. Liver- more, and Julian R. Rachele. Synthetic benzylpenicillin. In: The Chemistry of Penicillin, ed. Hans T. Clarke, John R. Johnson, and Sir Robert Robinson? pp. 1018-24. Princeton: Princeton Uni- versity Press. With Elizabeth B. Keller and Julian R. Rachele. A study of trans- methylation with methionine containing deuterium and carbon 14 in the methyl group. i. Biol. Chem., 177:733-38. With Cosmo G. Mackenzie. Formation of formaldehyde in the bio- logical oxidation of the methyl group of sarcosine. Fed. Proc. Fed. Am. Soc. Exp. Biol., 8:223. With Martha A. Ferger. The antiphenylalanine effect of p-2- thienylalanine for the rat. l. Biol. Chem., 179:61-65. With Cosmo G. Mackenzie, Joseph P. Chandler, Elizabeth B. Keller, Julian R. Rachele, and Nancy Cross. The oxidation and distri- bution of the methyl group administered as methionine. I. Biol. Chem., 180:99-111. With Arthur H. Livermore. Preparation of high potency oxytocic

578 BIOGRAPHICAL MEMOIRS material by the use of counter-current distribution. I. Biol. Chem., 180:365-73. With William R. Carroll and Gardner W. Stacy. cx-Ketobutyric acid as a product in the enzymatic cleavage of cystathionine. l. Biol. Chem., 180:375-82. With Lester I. Reed and A. R. Kidwai. Preparation of the optically active isomers of S-benzylhomocysteine by enzymatic resolu- tion. }. Biol. Chem., 180:571-74. With Lester }. Reed. Doriano Cavallini, Fred Plum, and Julian R. Rachele. The conversion of methionine to cystine in a human cystinuric. I. Biol. Chem., 180:783-90. With Roger A. Boissonnas and Robert A. Turner. Metabolic study of the methyl groups of butter yellow. I. Biol. Chem., 180: 1053-58. 1950 With John G. Pierce. Preliminary studies on the amino acid content of a high potency preparation of the oxytocic hormone of the posterior lobe of the pituitary gland. J. Biol. Chem., 182:359- 66. With Sofia Simmonds, Elizabeth B. Keller, and Joseph P. Chandler. The effect of ethionine on transmethylation from methionine to choline and creatine in viva. I. Biol. Chem., 183:191-95. With Walter G. Verly. Incorporation in vivo of C'4 from labeled methanol into the methyl groups of choline. I. Am. Chem. Soc., 72:1049. With Cosmo G. Mackenzie, Julian R. Rachele, Nancy Cross, and Joseph P. Chandler. A study of the rate of oxidation of the methyl group of dietary methionine. J. Biol. Chem., 183:617- 26. With Elizabeth B. Keller and Robert A. Boissonnas. The origin of the methyl group of epinephrine. I. B dol. Che m., 1 8 3 :62 7-3 ~ . With John E. Wilson. Inhibition of the growth of the rat by L- penicillamine and its prevention by aminoethanol and related compounds. }. Biol. Chem., 184:63-70. With Martha F. Ferger. Oxidation in vivo of the methyl groups of choline, betaine, dimethylthetin, and dimethyl-~-propiothetin. I. Biol. Chem., 185:53-57. With Cosmo G. Mackenzie. Biochemical stability of the methyl group of creatine and creatinine. l. Biol. Chem., 185: 185-89.

VINCENT DU VIGNEAUD 579 With Walter G. Verly and John Eric Wilson. Incorporation of the carbon of formaldehyde and formate into the methyl groups of choline. i. Am. Chem. Soc., 72:2819-20. With Julian R. Rachele, Lester }. Reed, A. R. Kidwai, and Martha F. Ferger. Conversion of cystathionine labeled with S35 to cystine in viva. I. Biol. Chem., 185:817-26. With John G. Pierce. Studies on high potency oxytocic material from beef posterior pituitary lobes. I. Biol. Chem., 186:77-84. With Charlotte Ressler and Julian R. Rachele. The biological syn- thesis of "labile methyl groups." Science, 112:267-71. 1951 With Robert A. Turner and John G. Pierce. Purification and amino acid content of presser principle (vasopressin) of posterior lobe of the pituitary. Fed. Proc. Fed. Am. Soc. Exp. Biol., 10:261. With Walter G. L. Verly, John E. Wilson, Julian R. Rachele, Char- lotte Ressler, and John M. Kinney. One-carbon compounds in the biosynthesis of the "biologically labile" methyl group. J. Am. Chem. Soc., 73:2782-85. With Robert A. Turner and John G. Pierce. The purification and the amino acid content of vasopressin preparation. I. Biol. Chem., 191:21-28. With Tohannes M. Mueller, John G. Pierce, and Helen Davoll. The oxidation of oxytocin with performic acid. I. Biol. Chem., 191 :309-13. With Charlotte Ressler, Julian R. Rachele, James A. Reyniers, and Thomas D. Luckey. The synthesis of "biologically labile" methyl groups in the germ-free rat. I. Nutr., 45:361-76. With Robert A. Turner and John G. Pierce. The desulfurization of oxytocin. I. Biol. Chem., 193:359-61. With Helen Davoll, Robert A. Turner, and John G. Pierce. An in- vestigation of the free amino groups in oxytocin and desulfur- ized oxytocin preparations. J. Biol. Chem., 193:363 -70. 1952 With Cosmo G. Mackenzie. The effect of choline and cystine on the oxidation of the methyl group of methionine. J. Biol. Chem., 195 :487-91. With Walter G. Verly and John M. Kinney. Effect of folic acid and

580 BIOGRAPHICAL MEMOIRS leucovorin on synthesis of the labile methyl group from meth- anol in the rat. }. Biol. Chem., 196: 19-23. With Charlotte Ressler and Julian R. Rachele. Studies in vivo on labile methyl synthesis with deuterio-C~4-formate. i. Biol. Chem., 197: 1-5. With Edwin A. Popenoe and H. Claire Lawler. Partial purification and amino acid content of vasopressin from hog posterior pi- tuitary glands. i. Am. Chem. Soc., 74:3713. With Edwin A. Popenoe, John G. Pierce, and H. B. van Dyke. Ox- ytocic activity of purified vasopressin. Proc. Soc. Exp. Biol. Med., 81:506-8. With John G. Pierce and Samuel Gordon. Further distribution studies on the oxytocic hormone of the posterior lobe of the pituitary gland and the preparation of an active crystalline fla- vianate. J. Biol. Chem., 199:929-40. With Walter G. Verly, Julian R. Rachele, Maxwell L. Eidinoff, and Joseph E. Knoll. A test of tritium as a labeling device in a bio- logical study. T. Am. Chem. Soc., 74:5941-43. 1953 With Henry G. Kunkel and Sterling P. Taylor, fir. Electrophoretic properties of oxytocin. i. Biol. Chem., 200:559-64. With Sterling P. Taylor, ir., and Henry G. Kunkel. Electrophoretic studies of oxytocin and vasopressin. Fed. Proc. Fed. Am. Soc. Exp. Biol., 12:279-80. With John M. Kinney, John E. Wilson, and Julian R. Rachele. Effect of the presence of labile methyl groups in the diet on labile methyl neogenesis. Biochim. Biophys. Acta, 12:88-91. With Johannes Mueller and {ohn G. Pierce. Treatment of per- formic acid-oxidized oxytocin with bromine water. i. Biol. Chem., 204:857-60. With Charlotte Ressler and Stuart Trippett. Free amino groups of performic acid-oxidized oxytocin and its cleavage products formed by treatment with bromine water. i. Biol. Chem., 204:861-69. With Carleton W. Roberts. The synthesis of 0-sulfo-L-alanyl-L- tyrosine and L-tyrosyl-L-cysteic acid and their dibromotyrosyl analogues. i. Biol. Chem., 204:871-75. With Charlotte Ressler, John M. Swan, Carleton W. Roberts, Pan

VINCENT DU VIGNEAUD 581 ayotis G. Katsoyannis, and Samuel Gordon. The synthesis of an octapeptide amide with the hormonal activity of oxytocin. I. Am. Chem. Soc., 75:4879-80. With H. Claire Lawler and Edwin A. Popenoe. Enzymatic cleavage of glycinamide from vasopressin and a proposed structure for this pressor-antidiuretic hormone of the posterior pituitary. i. Am. Chem. Soc., 75:4880-81. With H. Claire Lawler. Enzymatic evidence for the intrinsic oxy- tocic activity of the pressor-antidiuretic hormone. Proc. Soc. Exp. Biol. Med., 84: 114-16. With Sterling P. Taylor, Tr., and Henry G. Kunkel. Electrophoretic studies of oxytocin and vasopressin. I. Biol. Chem., 205:45-53. With Edwin A. Popenoe. Degradative studies on vasopressin and performic acid-oxidized vasopressin. I. Biol. Chem., 205:133- 43. With Charlotte Ressler and Stuart Trippett. The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. i. Biol. Chem., 205:949-57. With Samuel Gordon. Preparation of S,S'-dibenzyloxytocin and its reconversion to oxytocin. Proc. Soc. Exp. Biol. Med., 84: 723-25. 1954 With Edwin A. Popenoe. A partial sequence of amino acids in per- formic acid-oxidized vasopressin. i. Biol. Chem., 206:353-60. Some studies on the active principles of the posterior pituitary gland. Harvard Memoirs, 3:65. With Kenneth Nickerson, Roy W. Bonsnes, R. Gordon Douglas, and Peter Condliffe. Oxytocin and milk ejection. Am. I. Obstet. Gynecol., 67: 1028-34. With Charlotte Ressler. The synthesis of the tetrapeptide amide S- benzyl-L-cysteinyl-L-prolyl-L-leucvl~lvcinamide. I. Am. Chem. . _ ~ _ ~ _ ~ _ _ _ ~ _ _ _ ~A Soc., 76:3107-9. With John W. Swan. The synthesis of L-glutaminyl-L-asparagine, L-glutamine and L-isoglutamine from p-toluenesulfonyl-L- glutamic acid. I. Am. Chem. Soc., 76:3110-13. With Panayotis G. Katsoyannis. The synthesis of p-toluenesulfonyl- L-isoleucyl-L-glutaminyl-L-asparagine and related peptides. J. Am. Chem. Soc., 76:3113-15.

582 BIOGRAPHICAL MEMOIRS With Charlotte Ressler, John M. Swan, Carleton W. Roberts, and Panayotis G. Katsoyannis. The synthesis of oxytocin. J. Am. Chem. Soc., 76:3115-21. With Duane T. Gish and Panayotis G. Katsoyannis. A synthetic preparation possessing biological properties associated with ar- ginine-vasopressin. I. Am. Chem. Soc., 76:4751-52. With Edwin A. Popenoe. Synthesis of L-phenylalanyl-L-gluta- minyl-L-asparagine. I. Am. Chem. Soc., 76:6202-3. With Charlotte Ressler. Bromination of performic acid-oxidized oxytocin. i. Biol. Chem., 211:809-14. With H. Claire Lawler, Sterling P. Taylor, and Ailsa h1. Swan. Pres- ence of glutamine and asparagine in enzymatic hydrolysates of oxytocin and vasopressin. Proc. Soc. Exp. Biol. Med., 87:550- 52. 1955 . With Julian R. Rachele, Edward }. Kuchinskas, and F. Howard Kratzer. Hydrogen isotope effect in the oxidation in viva of methionine labeled in the methyl group. I. Biol. Chem., 215: 593-601. With R. Gordon Douglas and Roy W. Bonsnes. Natural and syn- thetic oxytocin. Obstet. Gynecol., 6:254-57. With D. Wayne Woolley, Robert B. Merrifield, and Charlotte Res- sler. Strepogenin activity of synthetic peptides related to oxy- tocin. Proc. Soc. Exp. Biol. Med., 89:669-73. The synthesis of cystine peptides with special reference to the syn- thesis of oxytocin. Chem. Soc. Spec. Publ. no. 2. ()xytoc~n, the principal oxytocin hormone of the posterior pitui- tary gland: Its isolation, structure, synthesis. Experientia Suppl. 2:9. Hormones of the posterior pituitary gland: Oxytocin and vaso- pressin. Harvey Lect. Ser. L: 1-25.  The isolation and proof of structure of the vasopressins and the synthesis of octapeptide amides with pressor-antidiuretic activ- ity. Proc. 3d Int. Congr. Biochem., Brussels, pp. 49-54. 1956 Trail of sulfur research: From insulin to oxytocin. Science, 123: 967-74.

VINCENT DU VIGNEAUD 583 With M. Frederick Bartlett, Albert iohl, Roger Roeske, R. l. Sted- man, F. H. C. Stewart, and Darrell N. Ward. Studies on the syn- thesis of lysine-vasopressin. ]. Am. Chem. Soc., 78:2905-6. With Panayotis G. Katsoyannis. Synthesis of S-benzyl-N-carbobenz- oxy - L- cysteinyl - L - tyrosyl - L- phenylalanyl - L - glutaminyl - L - as- paragine, a pentapeptide derivative related to vasopressin. I. Am. Chem. Soc., 78:4482-83. With Darrell N. Ward. Studies on the purification of lysine vaso- pressin from hog pituitary glands. J. Biol. Chem., 222:951-58. With Julian R. Rachele and Alan M. White. A crucial test of trans- methylation in viva by intramolecular isotopic labeling. }. Am. Chem. Soc., 78:5131-32. With Roger Roeske, F. H. C. Stewart, and R. I. Stedman. Synthesis of a protected tetrapeptide amide containing the carboxyl ter- minal sequence of lysine-vasopressin, }. Am. Chem. Soc., 78: 5883-87. A trail of sulfur research: From insulin to oxytocin. In: Les Prix Nobel en 1955, pp. 446-65. Stockholm: Jungl. Boktr. P. A. Nor- stedt and Soner. 1957 With Edward I. Kuchinskas. An increased vitamin B6 requirement in the rat on a diet containing L-penicillamine. Arch. Biochem. Biophys., 66:1-9. With Edward }. Kuchinskas and Antonio Horvath. An anti-vitamin Be action of L-penicillamine. Arch. Biochem. Biophys., 68:69- 75. With Duane T. Gish. Synthesis of peptides of arginine related to arginine-vasopressin. i. Am. Chem. Soc., 79:3579. With Edward }. Kuchinskas and Antonio Horvath. L-penicillamine and rat liver transaminase activity. Arch. Biochem. Biophys., 69: 130-37. With Charlotte Ressler. The isoglutamine isomer of oxytocin: Its synthesis and comparison with oxytocin. l. Am. Chem. Soc., 79:4511-15. With Panayotis G. Katsoyannis and Duane T. Gish. Synthetic stud- ies on arginine vasopressin condensation of S-benzyl-N-carbo- benzoxy - L- cysteinyl - L - tyrosyl - L - phenylalanyl - L - glutaminyl - L-asparagine and its O-tosyl derivative with S-benzyl-L

584 BIOGRAPHICAL MEMOIRS cysteinyl-L-prolyl-L-arginyl-glycinamide. J. Am. Chem. Soc., 79:4516-20. With M. Frederick Bartlett and Albert total. The synthesis of lysine vasopressin. I. Am. Chem. Soc., 79:5572-75. With Albert Light and Roger Acher. Ion exchange chromatogra- phy of purified posterior pituitary preparations. J. Biol. Chem., 228:633-41. 1958 With Thomas F. Dillon, B. E. Marbury, Roy W. Bonsnes, and R. Gordon Douglas. Vasopressin as a hemostatic in gynecologic surgery. Obstet. Gynecol., 11:363-71. With Panayotis G. Katsoyannis, Duane T. Gish, and George P. Hess. Synthesis of two protected hexapeptides containing the N- terminal and C-terminal sequences of arginine-vasopressin. I. Am. Chem. Soc., 80:2558-62. With Roger Acher and Albert Light. Purification of oxytocin and vasopressin by way of a protein complex. J. Biol. Chem., 233:116-20. With Duane T. Gish, Panayotis G. Katsoyannis, and George P. Hess. Synthesis of the pressor-antidiuretic hormone, arginine-vaso- pressin. i. Am. Chem. Soc., 80:3355-58. With Albert Light. On the nature of oxytocin and vasopressin from human pituitary. Proc. Soc. Exp. Biol. Med., 98:692-96. With Panayotis G. Katsoyannis. Arginine-vasotocin, a synthetic an- alogue of the posterior pituitary hormones containing the ring of oxytocin and the side chain of vasopressin. i. Biol. Chem., 233: 1352-54. With Panayotis G. Katsoyannis. The synthesis of the histidine ana- log of the vasopressins. Arch. Biochem. Biophys., 78:555-62. 1959 With Wilson B. Lutz, Charlotte Ressler, and Donald E. Nettleton, Jr. Isoasparagine-oxytocin: The isoasparagine isomer of oxy- tocin. }. Am. Chem. Soc., 81:167-74. With Miklos Bodanszky. Synthesis of a biologically active analog of oxytocin, with phenylalanine replacing tyrosine. ~. Am. Chem. Soc., 81: 1258-59. .

VINCENT DU VIGNEAUD 585 With Miklos Bodanszky. An improved synthesis of oxytocin. I. Am. Chem. Soc., 81:2504-7. With Miklos Bodanszky. Synthesis of oxytocin by the nitrophenyl ester method. Nature, 183: 1324-25. With Albert Light and Rolf Studer. Isolation of oxytocin and ar- ginine vasopressin by way of a protein complex on a preparative scale. Arch. Biochem. Biophys., 83:84-87. With Miklos Bodanszky. A method of synthesis of long peptide chains using a synthesis of oxytocin as an example. J. Am. Chem. Soc., 81:5688-91. With Miklos Bodanszky. Synthesis of a biologically active analog of oxytocin, with phenylalanine replacing tyrosine. J. Am. Chem. Soc., 81:6072-75. With Panayotis G. Katsoyannis. Arginine vasotocin. Nature, 184: 1465. With Miklos Bodanszky. A new crystalline salt of oxytocin. Nature, 184:981-82. 1960 With Rolf Studer. Synthetic work related to arginine-vasopressin. i. Am. Chem. Soc., 82:1499-1501. With Johannes Meienhofer. Preparation of lysine-vasopressin through a crystalline protected nonapeptide intermediate and purification of the hormone by chromatography. }. Am. Chem. Soc., 82:2279-82. With Thomas F. Dillon, R. Gordon Douglas, and M. L. Barber. Transbuccal administration of pitocin for induction and stim- ulation of labor. Obstet. Gynecol., 15: 587-92. With Miklos Bodanszky and Johannes Meienhofer. Synthesis of Ivsine-vasonressin by the nitrophenyl ester method. i. Am. Chem. Soc., 82:3195-98. Experiences in the polypeptide field: Insulin to oxytocin. Ann. N.Y. Acad. Sci., 88:537-48. With Harry D. Law. Synthesis of 2-p-methoxyphenylalanine oxy- tocin (O-methyl-oxytocin) and some observations on its phar- macological behavior. I. Am. Chem. Soc., 82:4579-81. With Peter S. Fitt, Miklos Bodanszky, and Maureen O'Connell. Syn- thesis and some pharmacological properties of a peptide deriv

586 BIOGRAPHICAL MEMOIRS alive of oxytocin: Glycyloxytocin. Proc. Soc. Exp. Biol. Med., 104:653-56. With Gershen Winestock, V. V. S. Murti, Derek B. Hope, and Ray- mond D. Kimbrough, in Synthesis of 1-~-mercaptopropionic acid oxytocin (desaminooxytocin), a highly potent analogue of oxytocin. }. Biol. Chem., 235:PC64-66. With Johannes Meienhofer. Synthesis of a biologically active analog of lysine-vasopressin, with phenylalanine replacing tyrosine: 2- Phenylalanine lysine-vasopressin. i. Am. Chem. Soc., 82:6336- 37. 1961 With Johannes Meienhofer. Synthesis of a lysine-vasopressin deriv- ative with a methyl substituent on the imino nitrogen of the peptide bond between lysine and glycinamide (9-sarcosine lys- ine-vasopressin). I. Am. Chem. Soc., 83:142-45. With Raymond D. Kimbrough, Jr. Lysine-vasotocin, a synthetic an- alogue of the posterior pituitary hormones containing the ring of oxytocin and the side chain of lysine-vasopressin. T Biol. Chem., 236:778-80. With Derek iarvis and Miklos Bodanszky. The synthesis of 1-(hemi- homocystine).oxytocin and a study of some of its pharma- cological properties. }. Am. Chem. Soc., 83:4780-84. . 1962 With Conrad H. Schneider, Tohn E. Stouffer, V. V. S. Murti, tan- ardan P. Aroskar, and Gershen Winestock. fritiation of oxyto- cin by the Wilzbach method and the synthesis of oxytocin from tritium-labelled leucine. ~. Am. Chem. Soc., 84:409-13. With William D. Cash, Logan McCulloch Mahaffey, Alfred S. Buck, Donald E. Nettleton, ir., and Christos Romas. Synthesis and biological properties of 9-sarcosine oxytocin. }. Med. Pharm. Chem., 5:413-23. With Derek B. Hope and V. V. S. Murti. A highly potent analogue of oxytocin, desamino-oxytocin. i. Biol. Chem., 237: 1563 -66. With Miklos Bodanszky. p-Nitrophenyl carbobenzoxyglycinate. - Biochem. Prep., 9: 110-12. With Conrad H. Schneider. Synthesis of D-leucine-oxytocin, a bio- logically active diastereoisomer of oxytocin, and demonstration

VINCENT DU VIGNEAUD 587 of its separability from oxytocin upon countercurrent distri- bution. I. Am. Chem. Soc., 84:3005-8. With Derek B. Hope. Synthesis of desamino-desoxy-oxytocin, a biologically active analogue of oxytocin. i. Biol. Chem., 237: 3146-50. With W. Y. Chan. Comparison of the pharmacologic properties of oxytocin and its highly potent analogue, desamino-oxytocin. Endocrinology, 71:977-82. With John E. Stouffer and Derek B. Hope. Neurophysin, oxytocin and desamino-oxytocin. In: Perspectives in Biology, ed. C. F. Cori, V. G. Foglia, L. F. Leloir, and S. Ochoa, pp.75-80. Amsterdam: Elsevier Publishing Company. With Thomas F. Dillon and R. Gordon Douglas. Further observa- tions on transbuccal administration of pitocin for induction and stimulation of labor. Obstet. Gynecol., 20:434-41. 1963 With Julius Golubow. Comparison of susceptibility of oxytocin and desamino-oxytocin to inactivation by leucine aminopeptidase and cx-chymotrypsin. Proc. Soc. Exp. Biol. Med., 112:218-19. With Raymond D. Kimbrough, Jr., William D. Cash, Luis A. Branda, and W. Y. Chan. Synthesis and biological properties of 1-desamino-8-lysine-vasopressin. I. Biol. Chem., 238:1411-14. With George S. Denning, Jr., Stefania Drabarek, and W. Y. Chan. The effect of replacement of the carboxamide group by hydro- gen in the glutamine or asparagine residue of oxytocin on its biological activity. }. Biol. Chem., 238:PC1560-61. With Julius Golubow and W. Y. Chan. Effect of human pregnancy serum on avian depressor activities of oxytocin and desamino- oxytocin. Proc. Soc. Exp. Biol. Med., 113:113-15. With Derek B. Hope and V. V. S. Murti. Synthesis of 1-hemi-D- cystine-oxytocin. }. Am. Chem. Soc., 85:3686-88. 1964 With t. P. Aroskar, W. Y. Chan, }. E. Stouffer, C. H. Schneider, and V. V. S. Murti. Renal excretion and tissue distribution of radio- activity after administration of tritium-labeled oxytocin to rats. Endocrinology, 74:226 -32. With Derek Tarvis. Crystalline deamino-oxytocin. Science, 143: 545-48.

588 BIOGRAPHICAL MEMOIRS With George S. Denning, Jr., Stefania Drabarek, and W. Y. Chan. The synthesis and pharmacological study of 4-decarboxamido- oxytocin (4-`x-aminobutyric acid-oxytocin) and 5-decarbox- amido-oxytocin (5-alanine-oxytocin). J. Biol. Chem., 239:472- 77. With julian R. Rachele, John E. Wilson, Fred Plum, and Lester I. Reed. The administration of radioactive L-cystathionine to a human cystinuric. Adv. Chem., 44:82. Significance of the chemical functional groups of oxytocin to its pharmacological activity. Abstr. 6th Int. Congr. Biochem., New York City:97-98. An organic chemical approach to the study of the significance of the chemical functional groups of oxytocin to its biological ac- tivities. Proc. 8th Robert A. Welch Found. Conf. Chem. Res. Selected Topics in Modern Biochemistry. 1965 With Julian R. Rachele. The concept of transmethylation in mam- malian metabolism and its establishment by isotopic labeling through in viva experimentation. In: Transmethylation and Me- thionine Biosynthesis, ed. Shapiro and Schlenk, pp. 1-20. Chi- cago: University of Chicago Press. With Iphigenia Photaki.4-Deamido-oxytocin, an analog of the hor- mone containing glutamic acid in olace of ~lutamine. I. Am. Chem. Soc., 87:908-9. . ~ With Miklos Bodanszky and George S. Denning, Jr. p-Nitrophenyl carbobenzoxy-L-asparaginate. Biochem. Prep., 10:122-25. The hormones of the posterior pituitary gland with special refer- ence to their milk-ejecting ability. Bull. N.Y. Acad. Med., 41: 802-3. With Donald Yamashiro and H. L. Aaning. Inactivation of oxytocin by acetone. Proc. Natl. Acad. Sci. USA, 54:166-71. With Derek Jarvis and Barbara M. Ferrier. The effect of increasing the size of the ring present in deamino-oxytocin by one meth- ylene group on its biological properties: The synthesis of 1-^y- mercaptobutyric acid-oxytocin. I. Biol. Chem., 240:3553-57. With Stefania Drabarek. 2-D-tyrosine-oxytocin and 2-D-tyrosine- deamino-oxytocin, diastereoisomers of oxytocin and deamino- oxytocin. J. Am. Chem. Soc., 87:3974-78.

VINCENT DU VIGNEAUD 589 With Maurice Manning.6-Hemi-D-cystine-oxytocin, a diastereoiso- mer of the posterior pituitary hormone oxytocin. J. Am. Chem. Soc., 87:3978-82. With Maurice Manning. 4-~-Alanine-oxytocin: An oxytocin analog containing a twenty-one-membered disulfide ring. Biochemis- try, 4:1884-87. With George Flouret. The synthesis of D-oxytocin, the enantiomer of the posterior pituitary hormone, oxytocin. }. Am. Chem. Soc., 87:3775-76. With Roderich Walter. 6-Hemi-L-selenocystine-oxytocin and 1- deamino-6-hemi-L-selenocystine-oxytocin, highly potent iso- logs of oxytocin and 1-deamino-oxytocin. }. Am. Chem. Soc., 87:4192-93. With Barbara M. Ferrier and Derek Carves. Deamino-oxytocin: Its isolation by partition chromatography on sephadex and crys- tallization from water, and its biological activities. }. Biol. Chem., 240:4264-66. 1966 With Barbara M. Ferrier. 9-Deamido-oxytocin, an analog of the hormone containing a glycine residue in place of the glycinam- ide residue. I. Med. Chem., 9:55-57. With Luis A. Branda. Synthesis and pharmacological properties of 9-decarboxamido-oxytocin. I Med. Chem., 9: 169 -72. With Donald Yamashiro and Dieter Gillessen. Simultaneous syn- thesis of 1-hemi-D-cystine-oxytocin and oxytocin and separa- tion of the diastereoisomers by partition chromatography on Sephadex by countercurrent distribution. I. Am. Chem. Soc., 88: 1310-13. With Roderich Walter. 1-Deamino-1,6-L-selenocystine-oxytocin, a highly potent isolog of 1-deamino-oxytocin. I. Am. Chem. Soc., 88: 1331-32. With George Flouret and Roderich Walter. Synthesis and some bio- logical properties of 4-valine-oxytocin and 1-deamino-4-valine- oxytocin. }. Biol. Chem., 241:2093-96. With Luis A. Branda and Stefania Drabarek. The synthesis and pharmacological properties of deamino-4-decarboxamido- oxytocin ~ 1-,3-mercaptopropionic acid-4-cx-aminobutyric acid- oxytocin). I. Biol. Chem., 241:2572-75.

590 BIOGRAPHICAL MEMOIRS With John l. Ferraro.7-D-proline-oxytocin and its deamino analog. Diastereoisomers of oxytocin and deamino-oxytocin. I. Am. Chem. Soc., 88:3847-50. With Horst Schulz. Synthesis of 1-L-penicillamine-oxytocin, 1-D- penicillamine-oxytocin, and 1-deaminopenicillamine-oxytocin. potent inhibitors of the oxytocic response of oxytocin. I. Med. Chem., 9:647-50. With Luis A. Branda. Deoxy-4-decarboxamido-oxytocin and deamino-deoxy-4-decarboxamidooxytocin. I. Biol. Chem., 241:4051-54. With Horst Schulz. The effect of replacing one of the hydrogens of the ,B-carbon of the p-mercaptopropionic acid residue in deamino-oxytocin by a methyl group on its oxytocic and avian vasodepressor activity. I. Am. Chem. Soc., 88:5015-18. With Donald Yamashiro and Dieter Gillessen. Oxytoceine and deamino-oxytoceine. Biochemistry, 5:3711-19. With Roderich Walter. 8-Alanine-oxytocin, 8-alanine-oxypressin, and their deamino analogs. Their synthesis and some of their pharmacological properties. Biochemistry, 5:3720-27. 1967 With Donald Yamashiro, Robert T. Havran, and H. L. Aanning. Inactivation of lysine-vasopressin by acetone. Proc. Natl. Acad. Sci. USA, 57: 1058-59. With Derek Jarvis. The effect of decreasing the size of the ring present in deamino-oxytocin by one methylene group on its biological properties: The synthesis of 1-mercaptoacetic acid- oxytocin. I. Biol. Chem., 242:1768-71. With Luis A. Branda and Victor l. Hruby. 2-Isoleucine-oxytocin and deamino-2-isoleucine-oxytocin: Their synthesis and some of their pharmacological activities. Mol. Pharmacol., 3:248-53. With Derek Jarvis and Maurice Manning. 1-Mercaptoacetic acid-4- ,B-alanine-oxytocin. Biochemistry, 6: 1223-30. With W. Y. Chan and Robert Fear. Some pharmacologic studies on 1-L-penicillamine-oxytocin and 1-deaminopenicillamine- osytocin: Two potent osytocin inhibitors. Endocrinology, 81: 1267-77. With Dieter Gillessen. The synthesis and pharmacological prop- erties of 4-decarboxamido-8-lysine-vasopressin, 5-decarbox

VINCENT DU VIGNEAUD 591 amido-8-lysine-vasopressin, and their 1-deamino analogues. }. Biol. Chem., 242:4806-12. With Horst Schulz. Synthesis and some pharmacological properties of 6-L-penicillamine-oxytocin. J. Med. Chem., 10: 1037-39. 1968 With Donald Yamashiro. Synthesis of"acetone-oxytocin" from an isopropylidene derivative of S-benzyl-L-cysteinyl-L-tyrosine. }. Am. Chem. Soc., 90:487-90. With Herbert Takashima and R. B. Merrifield. The synthesis of deamino-oxytocin by the solid phase method. I. Am. Chem. Soc., 90: 1323-25. With Donald Yamashiro and Derek B. Hope. Isomeric dimers of oxytocin. }. Am. Chem. Soc., 90:3857-60. With Donald Yamashiro, H. L. Aanning, Luis A. Branda, William D. Cash, and V. V. S. Murti. A synthesis of Fl-(N-methyl-hemi- L-cystine)~-oxytocin and a study of its reaction with acetone. I. Am. Chem. Soc., 90:4141-44. With W. Y. Chan, Victor J. Hruby, and George Flouret. 4-Leucine- oxytocin: A natriuretic, diuretic and anti-ADH polypeptide. Science, 161: 280-81. With Alfred T. Blomquist, Daniel H. Rich, Victor I. Hruby, Louis L. Nangeroni, and Paula Glose. Deuterated oxytocins. The syn- thesis and biological properties of three crystalline analogs of deamino-oxytocin deuterated in the 1-,3-mercaptopropionic acid position. Proc. Natl. Acad. Sci. USA, 61:688-92. With Victor I. Hruby and Donald Yamashiro. The structure of ace- tone-oxytocin with studies on the reaction of acetone with var- ious peptides. I. Am. Chem. Soc., 90:7106-10. Hormones of the mammalian posterior pituitary gland and their naturally occurring analogues. Johns Hopkins Med. J., 124:53- 65. With Robert T. Havran. The structure of acetone-lysine-vaso- pressin as established through its synthesis from the acetone derivative of S-benzyl-L-cysteinyl-L-tyrosine. I. Am. Chem. Soc., 91:2696-98. With Victor I. Hruby. The detection of a SchiE base intermediate in the formation of acetone-oxytocin. I. Am. Chem. Soc., 91 :3624-26.

592 BIOGRAPHICAL MEMOIRS With Robert T. Havran. The synthesis and pharmacological prop- erties of L2-isoleucinel-8-lysine-vasopressin and its 1-deamino analog. i. Am. Chem. Soc., 91:3626-28. With Victor }. Hruby and George Flouret. The synthesis and some of the pharmacological properties of L4-L-isoleucine]-oxytocin and t4-L-leucine]-oxytocin i. Biol. Chem., 244:3890-94. With Victor l. Hruby. Synthesis and some pharmacological activi- ties of t2-L-valinel-oxytocin and F2-L-leucine]-oxytocin. }. Med. Chem., 12:731-33. With Alfred T. Blomquist, Daniel H. Rich, Bruce A. Carlson, G. Ashley Allen, Victor }. Hruby, Herbert Takashima, Louis L. Nangeroni, and Paula Glose. Deuterated oxytocins: The syn- thesis and biological properties of a crystalline analog of de- amino-oxytocin deuterated in the 5-asparagine position. Proc. Natl. Acad. Sci. USA, 64:263-66. With George Flouret. The synthesis and some pharmacological activities of L4-L-norvaline]-oxytocin and L4-L-norleucine]- oxytocin and their deamino analogs. i. Med. Chem., 12:1035- 38. With Herbert Takashima and Wolfgang Fraefel. The synthesis and certain pharmacological properties of deamino-oxytocinoic acid methylamide and deamino-oxytocinoic acid dimethyl- amide. l. Am. Chem. Soc., 91:6182-85. 1970 With Herbert Takashima and Victor i. Hruby. The synthesis of ~ 1-deamino,4-L-leucine1-oxytocin and ~ 1-deamino,4-L-isoleu- cine]-oxytocin and some of their pharmacological properties. J. Am. Chem. Soc., 92:677-80. With Wolfgang Fraefel. The synthesis and pharmacological prop- erties of F1-~-mercaptovaleric acid)~-oxytocin, a homolog of deamino-oxytocin containing a twenty-two-membered ring. J. Am. Chem. Soc., 92:1030-32. With Victor }. H ruby and W. Y. Chan. t2,4-Diisoleucine]-oxytocin. An analog of oxytocin with natriuretic and diuretic activities. }. Med. Chem., 13: 185-87. With Herbert Takashima. The synthesis of deamino-oxytocinoic acid and acetone-oxytocinoic acid and their use in the prepa- ration of deamino-oxytocinoxyloxytocin and oxytocinoyloxy- tocin. }. Am. Chem. Soc., 92:2501-4.

VINCENT DU VIGNEAUD 593 With Dieter Gillessen. Synthesis and pharmacological properties of 4-decarboxamido-8-arginine-vasopressin and its 1-deamino analog. I. Med. Chem., 13:346-49. With Wolfgang Fraefel. L1-~-Mercaptoundecanoic acid)~-oxytocin, a 28-membered ring homolog of deamino-oxytocin. I. Am. Chem. Soc., 92:4426-27. With W. Y. Chan. Natriuretic, diuretic and anti-arginine-vasopres- sin (ADH) effects of two analogs of oxytocin: L4-Leucinel- oxytocin and L2,4-diisoleucine]-oxytocin. i. Pharmacol. Exp. Ther., 174:541 - 49. 1971 With George Flouret. Deamino-D-oxytocin. I. Med. Chem., 14: 556-57. With P. H. Von Dreele, A. I. Brewster, H. A. Scheraga, and M. F. Ferger. Nuclear magnetic resonance spectrum of lysine-vaso- pressin and its structural implications. Proc. Natl. Acad. Sci. USA, 68: 1028-31. With Victor i. Hruby and Martha F. Ferger. Synthesis and phar- macological properties of deaminotocinamide and a new syn- thesis of tocinamide. I. Am. Chem. Soc., 93:5539-42. With Jim D. Meador, Martha F. Ferger, G. Ashley Allen, and Alfred T. Blomquist. The synthesis and biological properties of L1- deaminopenicillaminel-oxytocin deuterated in the 1-position. Bioorg. Chem., 1: 123-28. 1972 With Myles A. Wille and W. Y. Chan. Solid phase synthesis of L3,4- dileucine]-oxytocin and a study of some of its pharmacological properties. i. Med. Chem., 15: 11 ~12. With Raymond I. Vavrek, Martha F. Ferger, G. Ashley Allen, Daniel H. Rich, and Alfred T. Blomquist. Synthesis of three oxytocin analogs related to L1-deaminopenicillamine1-oxytocin possess- ing antioxytocic activity. I. Med. Chem., 15: 123-26. With Martha F. Ferger, Warren C. ~ones, Jr., and Douglas F. Dyckes. Four cyclic disulfide pentapeptides possessing the ring of va- sopressin. }. Am. Chem. Soc., 94:982-84. With P. H. Von Dreele, A. I. Brewster, F. A. Bovey, H. A. Scheraga, and M. F. Ferger. Nuclear magnetic resonance studies of lysine- vasopressin: Structural constraints. Proc. Natl. Acad. Sci. USA, 68:3088-91.

594 BIOGRAPHICAL MEMOIRS With John D. Glass. Synthesis and certain pharmacological prop- erties of lysine-vasopressinoic acid methylamide and lysine- vasopressinoic acid dimethylamide. I. Med. Chem., 15:486-88. With Victor l. Hruby, Clark W. Smith, David K. Linn, and Martha F. Ferger. Synthesis and some pharmacological properties of tocinoic acid and deaminotocinoic acid. I. Am. Chem. Soc., 94:5478-80. With P. ~ Von Dreele, A. I. Brewster, l. Dadok, H. S. Scheraga, F. A. Bovey, and M. F. Ferger. Nuclear magnetic resonance spectrum of lysine-vasopressin in aqueous solution and its structural implications. Proc. Natl. Acad. Sci. USA, 69:2169- 73. With P. H. Von Dreele, H. A. Scheraga, D. F. Dyckes, and M. F. Ferger. Nuclear magnetic resonance spectrum of deamino- lysine-vasopressin in aqueous solution and its structural impli- cations. Proc. Natl. Acad. Sci. USA, 69:3322-26. 1973 With John D. Glass. Solid-phase synthesis and presser potency of ~ l-deamino-9-ethylenediamine]-lysine-vasopressin. }. Med. Chem., 16:160-61. With Douglas F. Dyckes, Martha F. Ferger, and W. Y. Chan. Syn- thesis and some of the pharmacological properties of t4- leucinel-8-lysine-vasopressin and ~ 1-deamino,4-leucinel-8-ly- sine vasopressin. }. Med. Chem., 1 6:843 - 47 . With Warren C. Tones, Tr., and John I. Nestor, fir. Synthesis and some pharmacological properties of ~ 1-deamino,9-thiogly- cineloxytocin. I. Am. Chem. Soc., 95:5677-79. 1974 With Douglas F. Dyckes, John I. Nestor, Jr., and Martha F. Ferger. ~ 1-~-Mercapto-,B,,8-diethylpropionic acid]-8-lysine-vasopressin, a potent inhibitor of 8-lysine-vasopressin and of oxytocin. J. Med. Chem., 17:250-52. With W. Y. Chan and Victor J. Hruby. Effects of magnesium ion and oxytocin inhibitors on the utertonic activity of oxytocin and prostaglandins E2 and F2a. I. Pharmacol. Exp. Ther., 190:77- 87. With W. Y. Chan, John I. Nestor, fir., and Martha F. Ferger. Inhi- bition of oxytocic responses to oxytocin in pregnant rats by

VINCENT DU VIGNEAUD 595 [ l-L-penicillamine]oxytocin and [ l-~-mercapto-,B,0-diethylpro- pionic acidjoxytocin. Proc. Soc. Exp. Biol. Med., 146:364-66. With Douglas F. Dyckes, John J. Nestor, Jr., Martha F. Ferger, and W. Y. Chan. [l-~-Mercapto-g,~-diethylpropionic acid, 4-leu- cinel-8-lysine-vasopressin and [1-~-mercapto-,13,,(3-diethylpro- pionic acid, 4-leucineloxytocin, compounds possessing antihor- monal properties. J. Med. Chem., 17 :969-71. With Douglas F. Dyckes, Clark W. Smith, and Martha F. Ferger. Synthesis and some pharmacological properties of [1-~- Maa]LVP and [l-l~y-MbalLVP. J. Am. Chem. Soc., 96:7549-51. 1975 With John J. Nestor, Jr., and Martha F. Ferger. [l-~-Mercapto-,(3,,8- pentamethylenepropionic acid]oxytocin, a potent inhibitor of oxytocin. J. Med. Chem., 18: 284-87. With J.J. Nestor, Jr., and M. F. Ferger. The retention of anti- oxytocic activity by the ring moieties of L 1-~-mercapto-p ,B-diethylpropionic acid]-oxytocin and [l-,B-mercapto-,l3,§-pen- tamethylenepropionic acidioxytocin. Proc. 4th Am. Peptide Symp., pp.755 - 59. Ann Arbor, Mich.: Ann Arbor Science Pub- lishers. ~, . ~. ~ 1976 With R. A. Plane. Reminiscences of a biochemist. J. Chem. Ed., 53:8-12.