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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
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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
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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
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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.
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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
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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
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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 . -
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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
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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
.
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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
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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
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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
OCR for page 587
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.
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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.
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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.
OCR for page 590
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
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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.
OCR for page 592
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.
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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.
OCR for page 594
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
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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.
Representative terms from entire chapter:
pharmacological properties
