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WILLIAM H
. STEIN
June 25, 1 91 1-February 2, 1 980
BY STANFORD MOORE
W~ ~ ~ ~ A M H . S T E ~ N began his autobiographical sketch
for the 1972 volume of Nobel lectures as follows:
I was born June 25, 1911, in New York City, the second of three children,
to Fred M. and Beatrice Borg Stein. My father was a businessman who was
greatly interested in communal affairs, particularly those dealing with
health, and he retired quite early in life in order to devote his full time to
such matters as the New York Tuberculosis and Health Association, Mon-
tefiore Hospital, and others. My mother, too, was greatly interested in
communal affairs and devoted most of her life to bettering the lot of th
children of New York City. During my childhood, I received much en-
couragement from both of my parents to enter into medicine or a fun-
damental science.
His early education was at the LincoIn School of the
Teachers College of Columbia University. It was a so-callecI
"progressive school" of the time; in addition to fostering in-
terest in the creative arts, music, writing, and sports, the cur-
riculum includecI well-taught courses in chemistry, physics,
and biology, with field trips that he enjoyed. From those
years, he used to recall that his first scientific project as a
student was as an avicI collector of moths and butterflies. At
sixteen, he transferred to a preparatory school in New En-
gland, Phillips Exeter Academy, which offered a clemanding
educational experience that he felt strengthened his work
habits and his precision of writing.
415
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416
BIOGRAPHICAL MEMOIRS
In 1929 he matriculated at Harvard, as had his father and
his older brother before him. He majored in chemistry; the
scientific background thus achieved led him to spend one
year as a grac;luate student at Harvard in chemistry. It was
suggested to him, however, that he might enjoy the devel-
oping subject of biochemistry more than organic chemistry
per se. As a result, in 1934 he transferred to the Department
of Biological Chemistry at the College of Physicians and Sur-
geons, Columbia University. He found the environment most
challenging. Hans Clarke, the chairman, hacI succeeded in
gathering a stimulating faculty and a group of unusually
giftec! graduate students from around the world. Nearly a
dozen of those students became outstandingly productive
biochemists.
During his graduate-student clays, in 1936, William Stein
married Phoebe Hockstader. His wife and their three sons
William H., fir.; David F.: and Robert T. were to be invalu-
able resources for a creative scientist throughout a career in
which science and family were intimately interwoven. Stein
lived on Manhattan most of his life, with an interlude in
Scarsdale, New York, while the children were of school age.
He enjoyoc! summer retreats both at Cos Cob, with oppor-
tunities for tennis and swimming, and, in the later years, at
WoocIbury, in Connecticut.
William Stein completecT his Ph.D. thesis in 1937, uncter
the guidance of E. G. Miller, Jr.; the subject was the amino
acid composition of elastin. Thus began a lifelong concern
with the chemistry of proteins. His first experiment was the
preparation of elastin from the ligamentum nuchae of the
ox. In the course of applying some of the gravimetric meth-
o(ls of the time, he used two precipitants that had been (le-
velopect by Max Bergmann potassium trioxalatochromiate
for glycine and ammonium rhodanilate for proline. He was
introcluced to these methods by Erwin Brand at Columbia,
who tract worked with Bergmann in Germany.
OCR for page 417
WILLIAM H. STEIN
417
Bergmann had arrived in the Unitec! States from Dresden
in 1934 to become a member of The Rockefeller Institute for
Meclical Research in New York. When Stein completer! his
studies for the Ph.D. clegree at Columbia in 1937, it was a
logical progression for him to move southward] on Manhattan
to join the Bergmann group. Again, Stein found himself in
an exceptionally stimulating environment; Bergmann was at-
tracting a talentect international group of postdoctoral assist-
ants, many of whom became prominent biochemists. Among
the current Academy members from this group are Joseph
S. Fruton, Emil L. Smith, Klaus Hofmann, ant! Paul Za
.
mecnik.
There were two main lines of investigation in the Berg-
mann laboratory: the specificity of proteolytic enzymes and
the structural chemistry of proteins. Stein initially applied his
talents to the task of trying to improve gravimetric methods
for amino acid determination. His first contribution to meth-
octology was his introduction of the concept of the solubility
product method in an attempt to permit quantitative results
to be obtained with reagents that gave sparingly soluble salts
of amino acids. Stanford Moore joined the Bergmann labo-
ratory in 1939, arriving via Vanclerbilt ant! Wisconsin. Berg-
mann suggested that Stein anc! Moore pool their efforts to
see whether the solubility product method could be clevel-
opec! into a practical analytical procedure. Through careful
attention to the details of gravimetric analysis, using two
of the reagents introduce by Bergmann, they were able
to determine glycine with 5-nitronaphthalene- i-sulfonic
acid as the precipitating agent and leucine with 2-bromo-
toluene-5-sulfonic acid. The method was applied to hyctro-
lysates of egg albumin and silk fibroin. But the future was
to provide methods that were to be less tedious anct more
micro.
At this stage, the research on amino acid! analysis was in-
terrupted by the war years. The laboratory was engaged
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418
BIOGRAPHICAL MEMOIRS
under contract to the Office of Scientific Research and De-
velopment to look for possible therapeutic agents for vesicant
war gases through stu(ly of the physiological mechanisms of
action of mustard gas and the nitrogen mustards. Stein was
a coauthor of a series of fundamental papers concerned with
the chemistry of the reactions of mustard gas and related
compounds with the functional groups of amino acids and
peptides.
During the war years, in 1944, illness took the life of Max
Bergmann at the age of fifty-eight. The members of the lab-
oratory carried the war work to completion in 1945, at which
time most of them moved on to other positions.
For three years, Moore hac! been out of the laboratory
~ (A
. ,~
serving the Office of Scientific Research and Development in
administrative capacities in Washington ant! on other war-
time assignments. Stein and Moore debatecT whether to ac-
cept appointments elsewhere or to ask the Director of The
Rockefeller Institute, Herbert S. Gasser, whether he would
give them a chance to see what they could accomplish on the
Rockefeller scene. Gasser offered the two young investigators
an opportunity, on a trial basis, to initiate a research program
that might merit continuccI support.
With that challenge, they starte(1 with the premise, born
of the Bergmann years, that accurate establishment of the
amino acid compositions of proteins is a first step toward
progress in determination of their chemical structures. In
1945 it was possible to take a completely new look at the
problem of amino acid analysis. The renaissance in chro-
matography stimulate(1 by A. J. P. Martin anti R. L. M. Synge
in England, together with Lyman C. Craig's development of
liquid-liquic! countercurrent distribution in his laboratory
just clown the corridor from the Bergmann department at
Rockefeller, brought to the attention of biochemists the
potential resolving power of multi-plate separations. After
OCR for page 419
WILLIAM H. STEIN
419
weighing the possibilities for speed, resolution, simplicity,
and quantitativeness, Stein and Moore cleciclect to try column
chromatography. Thus began several busy years of close col-
laborative effort on the clevelopment of methods ant! equip
ment.
.
After initial experiments in which the fractions were col-
lectect by hand, a photoelectric cirop-counting fraction col-
lector was built to expedite the collection of the effluent in a
series of small fractions of precise volume; it was the proto-
type for the commercially built fraction collectors based upon
this principle that became wiclely user! in biochemistry. Then
a simple and sensitive quantitative method for measuring the
concentration of amino acid in each tube was needed. The
ninhyctrin reaction hac! been introcluced by Ruhemann in
1911~. The blue-colored product is sensitive to oxidation; in
initial trials the results did not obey Beer's law. When the
reaction was carried out anaerobically, the yielct was im-
provec! and linearity was approached, but such a procedure
was inconvenient. An oxygen-free environment in solution
in an open tube was attained by including a dissolved reduc-
ing agent, such as stannous chloride or the recluced form of
ninhydrin (hydrinciantin). A water-miscible organic solvent
(first, methyl Cellosolve, and later, dimethy! sulfoxide) was
aciclec! to keep the blue-colored reaction product (diketohy-
drindyliclene-diketohydrinciamine) and hydrinciantin in so-
lution. This method of measurement was first used to mon-
itor the peaks elutecT from columns of potato starch operated
with n-butanol-water as the solvent system, a type of chro-
matogram first tried by Synge. With a neutral solvent, the use
of a preliminary wash with S-hyciroxyquinoline was found
essential to prevent metals in the starch from distorting the
separations. Over a period of several years, quantitative sys-
tems with starch columns were clevelopecl for determining all
of the common amino acids of protein hydrolysates and were
.
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420
BIOGRAPHICAL MEMOIRS
appliect to the analysis of ,E\-lactogIobulin and bovine serum
albumin in 1949. The results were welcome, but it took two
weeks to run the three starch columns required.
Faster analyses became possible when finely powdered ion
exchange resins became available for chromatography. With
1 fin . 1 1
.
sul~onatea polystyrene resins, several years ot exploratory
chromatograms lee! to the use of buyers of different pHs at
different temperatures for the serial elusion of all of the com-
mon amino acids of proteins and of physiological fluicts. In
the early 1950s, the time for each analysis was reclucect to
about five clays.
With an efficient chromatographic method at hand, the
next stage was to render the process automatic. This project
in instrumentation was undertaken in cooperation with Dar-
re! Spackman and lecl to an automatic amino acid analyzer
in 1958. The eluent was pumped through the resin bed at
several atmospheres of pressure. The ninhycirin color was
cleveloped in the flowing stream and the optical density was
recordecl potentiometrically; a hy(lrolysate was analyzecl in
an overnight run. Subsequent academically ant! commer-
cially introduced improvements have utilizer! finer resins and
higher pressures and have attained sixty-minute analyses.
The resulting amino acid analyzers found a worIc~wicle mar-
ket and represented the first wiclely used form of high-
performance liquid chromatography.
In the writing of the papers on methoclology every effort
was made to include all of the details needled for elective use
of the methods. This enterprise was facilitatect by circulating
preprints to biochemists who expresses! an immediate inter-
est in using the procedures and who could check the com-
pleteness of the experimental directions in advance of pub
. .
Cation.
During the early years of our cooperation, Stein anct I
worked out a system of collaboration that lasted for a lifetime.
OCR for page 421
WILLIAM H. STEIN
42
Stein combined an inventive mine! and a creep dedication to
science with great generosity. Over a period of forty years,
we approached problems with somewhat different perspec-
tives and then focused our thoughts on the common aim. If
~ die! not think of something, he was likely to, and vice versa,
and this process of frequent interchange of ideas accelerated
progress in research. It also helped in the writing of papers.
never ciraftect a text that Stein could not improve.
The methodology was developed with the primary aim in
mind of opening new approaches to the study of the chemical
structures of proteins. After the first four years of the above
studies, Gasser decided that the two young investigators were
making enough progress to merit being hosts to a postctoc-
toral fellow. In 1949, they attracted Werner Hirs from Co-
lumbia University. A key decision at that time was the choice
of the protein to study. In Englancl, Frederick Sanger hac!
his classic studies on insulin well uncler way, for which he was
able to use qualitative methods in large part. The study of
longer polypeptide chains wouIc! gain from quantitative anal-
yses at each step. And an enzyme would be an appealing
subject for stucly because the structural knowledge couict
provide a baseline for determination of specific residues in-
volved in the enzyme-substrate interactions. Bovine pan-
creatic ribonuclease, a protein about twice the size of insulin,
was readily available ant] had been partially purified at
Rockefeller by Dubos and Thompson and by Kunitz. Hirs
extended the technique of ion exchange chromatography to
ribonuclease on a polymethacrylic acid resin.
In 1952 Gasser clecided that Stein and Moore qualifier! as
members of The Rockefeller Institute for Medical Research;
the title became professor when the institution assumed its
role in graduate education as The Rockefeller University
under the administration of DetIev Bronk.
The research on chromatographically purified RNase A
OCR for page 422
422
BIOGRAPHICAL MEMOIRS
was then extended, with Hirs, to the development of meth-
ods for the ion exchange chromatography of peptides ob-
tained by tryptic and chymotryptic hydrolysis of the chain in
which the four disulfide bonds had been split by oxiclation.
I. Leggett Bailey joined the oroiect to stud the nentides lib
1 J J 1 1
eratec' oy pepsin. Thus began the collection of data from
which a sequence for the enzyme could be deduced, with the
invaluable additional aid of the sequential degradation re-
action newly introduced by Pehr Eciman in Sweden in 1950.
At the time that these studies on ribonuclease were begun,
Christian B. Anfinsen and his associates at NIH also turned
to ribonuclease as an appropriate molecule for structural
study; the combined results from the two laboratories (ex-
periments in progress were freely discussed) expedited the
solution of the problem. The determination of the final se-
quence, to which Darre} Spackman and Derek Smyth were
contributors at Rockefeller, also dependec1 upon a key obser-
vation at NTH by Erhard Gross and Bernhard Witkop, ob-
tained through the application of their ingenious method of
cleavage at methionine residues by cyanogen bromide. Thus,
for the first time, the chemical formula of an enzyme could
be written.
Derivatization experiments were then undertaken at
Rockefeller in order to identify residues at or near the active
site. Todoacetate was the first reagent studied. The enzyme
was known to be inactivated by the reagent; at that time rapid
reaction with iodoacetate was thought of primarily as an in-
dication of-SH groups. When it was established that ribo-
nucicase did not have any-SH groups, an evident task was
to ascertain what was happening. Through experiments be-
gun by Gerd GundIach' amino acid analysis was used to show
that, depending upon pH, the reagent could alkylate pri-
marily methionine, histidine, or lysine residues in the en-
zyme. Arthur Crestfield showed that in thirty minutes at pH
5.5, the principal reaction was with the imidazole group of
OCR for page 423
WILLIAM H. STEIN
423
one of two specific histicline residues, yielding a carboxy-
methy] group either on the I-nitrogen of histidine- ~ 19 or on
the 3-nitrogen of histidine-12. Through Robert Heinrikson's
ciata on the effect of carboxymethylation of the e-NH2 group
of {ysine-41 on these reactions, it was possible to conclucle
that in the three-ctimensional structure of the enzyme the
reactive nitrogens of histidine- 12 ant! histicline- ~ ~ 9 were
about 5 Angstroms apart at the active site of the catalyst and
that the s-NH2 group of lysine-41 was 7-10 Angstroms from
nitrogen-3 of histidine-12. These three-dimensional predic-
tions, macle on chemical grounds, were borne out by the sub-
sequent x-ray crystallographic analyses of Frederic Richards
and HaroIct Wyckoff at Yale.
One of the questions posed to George Stark was whether
these two uniquely reactive histidine residues would still be
especially reactive toward iodoacetate if the molecule were
unfolded in ~ M urea. As expected, they are not. But in one
of these experiments he detected, by amino-acic! analysis, a
sicle reaction that turned out to be carbamylation of lysine
residues by traces of cyanate in the urea to give homocitrul-
line. This observation served as one of several reminders
that, as demonstrated in ~ X28 by WohIer, ammonium cyanate
and urea are in equilibrium. One of those thus remincled was
Anthony Cerami, then a student in another laboratory at
Rockefeller. Some years later, when he heard that urea was
being administerec! to patients with sickle cell anemia, he
wondered whether cyanate merited consideration as the pos-
sible active agent in such an experiment. He elicitec! the co-
operation of lames Manning, who had recently joined the
Stein and Moore laboratory. From the investigations of the
two young men, there grew a decade of research on the ef-
fectiveness of the carbamylation of hemoglobin S in convert-
ing the molecule to one of almost normal physiological func-
tion.
From RNase A, with 124 amino acid residues, attention
OCR for page 424
424
BIOGRAPHICAL MEMOIRS
was turned to bovine pancreatic deoxyribonuclease; chro-
matography on phosphocellulose yiel(lect a homogeneous
preparation of DNase A, which proved to be a glycoprotein
with a single pepticle chain of 257 residues. The sequence of
DNase A was establishect in 1973 as a result of several years
of researches by Paul Price (as a graduate stuclent), Teh-yung
Liu, Brian Catley, Johann SaInikow, ant! Ta-hsiu Liao. Acldi-
tional experiments were conclucted by Tony Hugli, Bryce
Plapp, and Dalton Wang. The result was a thorough knowI-
edge of the chemistry of the enzyme, its existence in four
chromatographically distinct forms (A, B. C, and D), and
identification of special features of each isozyme.
Stein, throughout his life, in his generous manner, took a
special interest in facilitating the careers of scholars whose
sojourns in the laboratory made possible the exploration of
many facets of the researches. A number of enzymes were
the subjects of studies of specific aspects of protein structure
and function. For seventeen years, Stein was the principal
investigator on a grant from the National Institute of General
Medical Sciences, NIH, to study that subject. Some of the
enzymes, in actdition to RNase and DNase, that the labora-
tory stu(liecl with partial support from that grant were: bro-
melains (with Shoshi Ota), chymotrypsin (with Denis C.
Shaw), pepsin (with T. G. Rajagopalan, T. A. A. Dopheide,
and Roger Lundblad), streptococcal proteinase (with Teh-
yung Liu, William FerctinancI, Brenda Gerwin, Norbert Neu-
mann, Michael C. Lin, anti Michael Bustin, in cooperation
with the enzyme's discoverer, Stuart D. Elliott), ribonuclease
To (with Kenji Takahashi), 2',3'-cyclic nucleotide 3'-phos-
phohyctrolase from brain (with Arabinda Guha, David C. So-
gin, and Robert I. Drummond), and carboxypepticiase Y
(with Rikimaru Hayashi).
Stein took a particular interest in the application of the
chromatographic methods to the analysis of physiological
OCR for page 431
WILLIAM H. STEIN
1943
431
With Stanford Moore. Determination of amino acids by the solu-
bility product method. i. Biol. Chem., 150: 113 -30.
1944
With Stanford Moore and Max Bergmann. Aromatic sulfonic acids
as reagents for peptides. Partial hydrolysis of silk fibroid. }. Biol.
Chem., 154:191-201.
1946
Amino acid analysis of proteins. Introduction. Ann. N.Y. Acad. Sci.
47, Art. 2:59-62.
With Stanford Moore. The use of specific precipitants in the amino
acid analysis of proteins. Ann. N.Y. Acad. Sci. XLVII, Art.
2:95-118.
With Joseph S. Fruton and Max Bergmann. Chemical reactions
of the nitrogen mustard gases. V. The reactions of the nitro-
gen mustard gases with protein constituents. i. Org. Chem.,
11 :559-70.
With Joseph S. Fruton, Mark A. Stahmann, and Calvin Golumbic.
Chemical reactions of the nitrogen mustard gases. VI. The re-
actions of the nitrogen mustard gases with chemical compounds
of biological interest. I. Org. Chem., 11 :571-80.
With Stanford Moore and Max Bergmann. Chemical reactions of
mustard gas and related compounds. I. The transformations of
mustard gas in water. Formation and properties of sulfonium
salts derived from mustard gas. I. Org. Chem., 11 :664-74.
With Stanford Moore and Joseph S. Fruton. Chemical reactions of
mustard gas and related compounds. II. The reaction of mus-
tard gas with carboxyl groups and with the amino groups of
amino acids and peptides. I. Org. Chem., 11 :675-80.
With Stanford Moore. Chemical reactions of mustard gas and re-
lated compounds. III. The reaction of mustard gas with methi-
onine. i. Org. Chem., 11:681-85.
With Joseph S. Fruton. Chemical reactions of mustard gas and
related compounds. IV. Chemical reactions of {3-chloroethyl-D'-
hydroxyethylsulfide. J. Org. Chem., 11:686-91.
With Joseph S. Fruton and Max Bergmann. Chemical reactions of
OCR for page 432
432
BIOGRAPHICAL MEMOIRS
mustard gas and related compounds. V. The chemical reactions
of 1,2-bis (,3-chloroethyl)-sulfone, divinyl sulfone and divinyl
sulfoxide. i. Org. Chem., 11:719-35.
With Stephen M. Nagy, Calvin Golumbic, Joseph S. Fruton, and
Max Bergmann. The penetration of vesicant vapors into hu-
man skin. I. Gen. Physiol., 29:441-69.
1948
With Stanford Moore. Partition chromatography of amino acids
on starch. Ann. N.Y. Acad. Sci. 49, Art. 2:265-78.
With Stanford Moore. Chromatography of amino acids on starch
columns. Separation of phenylalanine, leucine, isoleucine, me-
thionine, tyrosine, and valine. i. Biol. Chem., 176:337-65.
With Stanford Moore. Photometric ninhydrin method for use in
the chromatography of amino acids. i. Biol. Chem., 176:367-
88.
1949
With Stanford Moore. Chromatography on amino acids on starch
columns. Solvent mixtures for the fractionation of protein hy-
drolysates. I. Biol. Chem., 178 :53-77.
With Stanford Moore. Amino acid composition of 13-lactoglobulin
and bovine serum albumin. i. Biol. Chem., 178:79-91.
1950
With Stanford Moore. Chromatographic determination of the
amino acid composition of proteins. Cold Spring Harbor Symp.
Quant. Biol., 14: 179-90.
1951
With Stanford
1951:35-41.
With C. H. W. Hirs and Stanford Moore. Chromatography of pro-
teins. Ribonuclease. i. Am. Chem. Soc., 73:1893.
With Stanford Moore. Electrolytic desalting of amino acids. Con-
version of arginine to ornithine. i. Biol. Chem., 190: 103-6.
With Harris H. Tallan. Studies on lysozyme. l. Am. Chem. Soc.,
73:2976.
With Stanford Moore. Chromatography of amino acids on sulfo-
nated polystyrene resins.~. Biol. Chem., 192:663-81.
Moore. Chromatography. Sci. Am., March,
.
OCR for page 433
WILLIAM H. STEIN
433
Excretion of amino acids in cystinuria. Proc. Soc. Exp. Biol. Med.,
78:705-8.
1952
With C. H. W. Hirs and Stanford Moore. Isolation of amino acids
by chromatography on ion exchange columns; use of volatile
buffers. }. Biol. Chem., 195:669-83.
With Stanford Moore. Chromatography. Annul Rev. Biochem.,
21:521-46.
1953
With C. H. W. Hirs and Stanford Moore. A chromatographic in-
vestigation of pancreatic ribonuclease. I. Biol. Chem.,200:493-
506.
With Harris H. Tallan. Chromatographic studies on lysozyme. }.
Biol. Chem., 200:507-14.
A chromatographic investigation of the amino acid constituents of
normal urine. I. Biol. Chem., 201:45-58.
1954
With Harris H. Tallan and Stanford Moore. 3-Methylhistidine, a
new amino acid from human urine. i. Biol. Chem., 206:825-
34.
With A. G. Bearn and Stanford Moore. The amino acid content of
the blood and urine in Wilson's disease. i. Clin. Invest. 33:410-
19.
With Alejandro C. Paladini, C. H. W. Hirs, and Stanford Moore.
Phenylacetylglutamine as a constituent of normal human urine.
I. Am. Chem. Soc., 76:2848.
With C. H. W. Hirs and Stanford Moore. The chromatography of
amino acids on ion exchange resins. Use of volatile acids for
elusion. i. Am. Chem. Soc., 76:6063-65.
With Stanford Moore. Procedures for the chromatographic deter-
mination of amino acids on four percent cross-linked sulfo-
nated polystyrene resins. l. Biol. Chem., 211:893-906.
With Stanford Moore. A modified ninhydrin reagent for the pho-
tometric determination of amino acids and related compounds.
I. Biol. Chem., 211:907-13.
With Stanford Moore. The free amino acids of human blood
plasma. }. Biol. Chem., 211:915-26.
OCR for page 434
434
BIOGRAPHICAL MEMOIRS
With Harris H. Tallan and Stanford Moore. Studies on the free
amino acids and related compounds in the tissues of the cat. }.
Biol. Them., 211 :927-39.
With C. H. W. Hirs and Stanford Moore. The amino acid compo-
sition of ribonuclease. }. Biol. Chem., 211:941-50.
1955
With Charles F. Crampton and Stanford Moore. Chromatographic
fractionation of calf thymus histone. i. Biol. Chem., 215:787-
801.
With Harris H. Tallan, S. Theodore Bella, and Stanford Moore.
Tyrosine-O-sulfate as a constituent of normal human urine. l.
Biol. Chem., 217:703 -8.
1956
With Harris H. Tallan and Stanford Moore. N-acetyl-L-aspartic
acid in brain. i. Biol. Chem., 219:257-64.
With C. H. W. Hirs and Stanford Moore. Peptides obtained by
tryptic hydrolysis of performic acid-oxidized ribonuclease. }.
Biol. Chem., 219:623-42.
With }. Leggett Bailey and Stanford Moore. Peptides obtained by
peptic hydrolysis of performic acid-oxidized ribonuclease. }.
Biol. Chem., 221:143-50.
With C. H. W. Hirs and Stanford Moore. Peptides obtained by
chymotryptic hydrolysis of performic acid-oxidized ribonu-
clease. A partial structural formula for the oxidized protein. }.
Biol. Chem., 221: 151-69.
With Stanford Moore and C. H. W. Hirs. Studies of structure of
ribonuclease. Fed. Proc. Fed. Am. Soc. Exp. Biol., 15:840-48.
With Stanford Moore. Column chromatography of peptides and
proteins. Adv. Protein Chem., 11: 191-236.
1957
With Charles F. Crampton and Stanford Moore. Comparative stud-
ies on chromatographically purified histones. }. Biol. Chem.,
225:363 -86.
With Henry G. Kunkel, R. David Cole, Darrel H. Spackman, and
Stanford Moore. Observations on the amino acid composition
of human hemoglobins. Biochim. Biophys. Acta, 24:640-42.
OCR for page 435
WILLIAM H. STEIN
435
1958
With Stanford Moore. Determination of the structure of proteins:
studies on ribonuclease. Harvey Lect., 52:119-43.
With Harris H. Tallan and Stanford Moore. L-cystathionine in hu-
man brain. ]. Biol. Chem., 230:707-16.
With Darrel H. Spackman and Stanford Moore. Automatic record-
ing apparatus for use in the chromatography of amino acids.
Anal. Chem., 30:1190-206.
With Stanford Moore and Darrel H. Spackman. Chromatography
of amino acids on sulfonated polystyrene resins. Anal. Chem.,
30:1185-90.
Observations of the amino acid composition of human hemoglo-
bins. Conference on hemoglobin. N.A.S.N.R.C. Publ., 557:
220-26.
With C. H. W. Hirs and Stanford Moore. Studies on the structure
of ribonuclease. In: IUPAC Symposium on Protein Structure, ed.
A. Neuberger, pp. 211-22. London: Methuen; New York: John
Wiley & Sons.
With Stanford Moore and Darrel H. Spackman. Automatic record-
ing apparatus for use in the chromatography of amino acids.
Fed. Proc. Fed. Am. Soc. Exp. Biol., 17:1107-15.
With R. David Cole and Stanford Moore. On the cysteine content
of human hemoglobin. }. Biol. Chem., 233: 1359-63.
With Stanford Moore, R. David Cole, and Gerd Gundlach. On the
cleavage of disulfide bonds in proteins by reduction. Proc. 4th
Int. Congr. Biochem., 8:52-62.
1959
With H. Gerd Gundlach and Stanford Moore. The nature of the
amino acid residues involved in the inactivation of ribonuclease
by iodoacetate. }. Biol. Chem., 234:1754-60.
With H. Gerd Gundlach and Stanford Moore. The reaction of io-
doacetate with methionine. i. Biol. Chem., 234: 1761-64.
1960
With C. H. W. Hirs and Stanford Moore. The sequence of the
amino acid residues in performic acid-oxidized ribonuclease. I.
Biol. Chem., 235:633-47.
With Darrel H. Spackman and Stanford Moore (with the assistance
OCR for page 436
436
BIOGRAPHICAL MEMOIRS
of Anna M. Zamoyska). The disulfide bonds of ribonuclease. J.
Biol. Chem., 235:648-59.
With M. Prince Brigham and Stanford Moore. The concentrations
of cysteine and cystine in human blood plasma. i. Clin. Invest.,
39: 1633-38.
With George R. Stark and Stanford Moore. Reactions of the cya-
nate present in aqueous urea with amino acids and proteins. J.
Biol. Chem., 235:3177-81.
Chemical modifications of ribonuclease. Brookhaven Symp. Biol.,
13: 104-14.
1961
With Stanford Moore. The chemical structure of proteins. Sci.
Am., 204:81-92.
With George R. Stark and Stanford Moore. Relationship between
the conformation of ribonuclease and its reactivity toward io-
doacetate. l. Biol. Chem., 236:436-42.
1962
With Norbert P. Neumann and Stanford Moore. Modification of
the methionine residues of ribonuclease. Biochemistry, 1:68-
75.
With Derek G. Smyth and Stanford Moore. On the sequence of
residues 11 to 18 in bovine pancreatic ribonuclease. I. Biol.
Chem., 237:1845-50.
With Arthur M. Crestfield and Stanford Moore. On the aggrega-
tion of bovine pancreatic ribonuclease. Arch. Biochem. Bio-
phys., Suppl. 1 :217-22.
1963
With Derek G. Smyth and Stanford Moore. The sequence of amino
acid residues of bovine pancreatic ribonuclease: revisions and
confirmations. i. Biol. Chem., 238:227-34.
With Arthur M. Crestfield and Stanford Moore. The preparation
and enzymatic hydrolysis of reduced and S-carboxymethylated
proteins. I. Biol. Chem., 238:622-27.
With Teh-Yung Liu, Norbert P. Neumann, Stuart I). Elliott, and
Stanford Moore. Chemical properties of streptococcal protein-
ase and its zymogen. I. Biol. Chem., 238:251-56.
OCR for page 437
WILLIAM H. STEIN
437
With Glyn Jones and Stanford Moore. Properties of chromato-
graphically purified trypsin inhibitors from lima beans. Bio-
chemistry, 2:66-71.
With Arthur M. Crestfield and Stanford Moore. On the prepara-
tion of bovine pancreatic ribonuclease A. l. Biol. Chem.,
238:618-21.
With Stanford Moore. Relationship between structure and activity
of ribonuclease. Proc. 5th Int. Congr. Biochem., 4:33-38.
With Arthur M. Crestfield and Stanford Moore. Alkylation and
identification of the histidine residues at the active site of ribo-
nuclease. }. Biol. Chem., 238:2413-20.
With Arthur M. Crestfield and Stanford Moore. Properties and
conformation of the histidine residues at the active site of ri-
bonuclease. }. Biol. Chem., 238:2421-28.
With Stanford Moore. Chromatographic determination of amino
acids by the use of automatic recording equipment. In: Methods
in Enzymology, ed. S. Colowick and H. Kaplan, vol. 6, pp. 819-
31. New York: Academic Press.
1964
With Shoshi Ota and Stanford Moore. Preparation and chemical
properties of purified stem and fruit bromelains. Biochemistry,
3: 180-85.
With Denis C. Shaw and Stanford Moore. Inactivation of chymo-
trypsin by cyanate. i. Biol. Chem., 239:671-73.
Structure-activity relationships in ribonuclease: the active site. 6th
Int. Congr. Biochem. Abstr., 32:243-44.
Structure-activity relationships in ribonuclease. Fed. Proc. Fed.
Am. Soc. Exp. Biol., 23:599-608.
With George R. Stark. Alkylation of the methionine residues of
ribonuclease in 8 M urea. i. Biol. Chem., 239:3755-61.
1965
With Teh-Yung Liu, Stanford Moore, and Stuart D. Elliott. The
sequence of amino acid residues around the sulfhydryl group
at the active site of streptococcal proteinase. ]. Biol. Chem.,
240:1143-49.
With William Ferdinand and Stanford Moore. An unusual disul-
fide bond in streptococcal proteinase. l. Biol. Chem.,240:1150-
55.
OCR for page 438
438
BIOGRAPHICAL MEMOIRS
With William Ferdinand and Stanford Moore. Susceptibility of re-
duced, alkylated trypsin inhibitors from lima beans to tryptic
action. Biochim. Biophys. Acta, 96:524-47.
With Robert L. Heinrikson, Arthur M. Crestfield, and Stanford
Moore. The reactivities of the histidine residues at the active
site of ribonuclease toward halo acids of different structures. i.
Biol. Chem., 240:2921-34.
The structure and the activity of ribonuclease. Isr. I. Med. Sci.
1: 1229-43.
1966
With Brenda I. Gerwin and Stanford Moore. On the specificity of
streptococcal proteinase. l. Biol. Chem., 241:3331 - 39.
With T. G. Rajogopalan and S. Moore. The inactivation of pepsin
by diazoacetylnorleucine methyl ester. J. Biol. Chem.,
241 :4295-97.
With T. G. Rajagopalan and S. Moore. Pepsin from pepsinogen.
Preparation and properties. i. Biol. Chem., 241:4940-50.
1967
With T. A. A. Dopheide and S. Moore. The carboxyl-terminal se-
quence of porcine pepsin. J Biol. Chem., 242: 1833-37.
With S. Moore and T.-Y. Liu. Structural studies of the proteinase
from group A streptococci. 7th Int. Congr. of Biochem. Abstr.,
11-12.
With T. A. A. Dopheide and S. Moore. Studies on the structure
and activity of pepsin. 7th Int. Congr. of Biochem. Abstr., 777.
With Kenji Takahashi and Stanford Moore. The identification of a
glutamic acid residue as part of the active site of ribonuclease
T. T Biol. Chem., 242:4682-90.
1968
With Michael C. Lin and Stanford Moore. Further studies on the
alkylation of the histidine residues at the active site of pan-
creatic ribonuclease. }. Biol. Chem., 243:6167-70.
With B. }. Catley and Stanford Moore. The carbohydrate moiety
of bovine pancreatic deoxyribonuclease. l. Biol. Chem.,
244:933-36.
OCR for page 439
WILLIAM H. STEIN
1969
439
With Roger L. Lundblad. On the reaction of diazoacetyl com-
pounds with pepsin. I. Biol. Chem., 244: 154-60.
With Paul A. Price, Teh-Yung Liu, and Stanford Moore. Properties
of chromatographically purified bovine pancreatic deoxyribo-
nuclease. I. Biol. Chem., 244:917-23.
With Paul A. Price and Stanford Moore. Alkylation of a histidine
residue at the active site of bovine pancreatic deoxyribonu-
clease. I. Biol. Chem., 244:924-28.
With Paul A. Price and Stanford Moore. Effect of divalent cations
on the reduction and reformation of the disulfide bonds of
deoxyribonuclease. i. Biol. Chem., 244:929-32.
1970
With Michael Bustin, Michael C. Lin, and Stanford Moore. Activity
of the reduced zymogen of streptococcal proteinase. }. Biol.
Chem., 245:846 -69.
Chemical studies on purified pepsin. In: International Symposium on
Structure-Function Relationships of Proteolytic Enzymes, ed. P. Des-
nuelle, H. Neurath, and M. Ottesen, pp. 253-60. New York:
Academic Press.
With Johann Salnikow and Stanford Moore. Comparison of the
multiple forms of bovine pancreatic deoxyribonuclease. I. Biol.
Chem., 245:5685-90.
1971
With Bryce V. Plapp and Stanford Moore. Activity of bovine pan-
creatic deoxyribonuclease A with modified amino groups. }.
Biol. Chem., 246:939-45.
With Tony E. Hugli. Involvement of a tyrosine residue in the ac-
tivity of bovine pancreatic deoxyribonuclease A. i. Biol. Chem.,
246:7191-200.
1973
With Johann Salnikow, Ta-Hsiu Liao, and Stanford Moore. Bovine
pancreatic deoxyribonuclease A. Isolation, composition, and
amino acid sequences of the tryptic and chymotryptic peptides.
I. Biol. Chem., 248:1480-88.
OCR for page 440
440
BIOGRAPHICAL MEMOIRS
With Ta-Hsiu Liao, Johann Salnikow, and Stanford Moore. Bovine
pancreatic deoxyribonuclease A. Isolation of cyanogen bromide
peptides; complete covalent structure of the polypeptide chain.
I. Biol. Chem., 248:1489-95.
With Rikimaru Hayashi and Stanford Moore. Carboxypeptidase
from yeast. Large scale preparation and the application to
COOH-terminal analysis of peptides and proteins. J. Biol.
Chem., 248:2296 -302.
With Stanford Moore. Chemical structures of pancreatic ribonu-
clease and deoxyribonuclease. Les Prix Nobel en 1972, pp.
120-43. Stockholm: The Nobel Foundation, and Science,
180:458-64.
With Rikimaru Hayashi and Stanford Moore. Serine at the active
center of yeast carboxypeptidase. J. Biol. Chem., 248:8366-69.
1974
With Jacques Bartholeyns and Stanford Moore. A pancreatic ri-
bonuclease active at pH 4.5. Int. }. Pept. Protein Res., 6:407-
17.
1977
With Jacques Bartholeyns, Dalton Wang, Peter Blackburn, Glynn
Wilson, and Stanford Moore. Explanation of the observation of
pancreatic ribonuclease activity at pH 4.5. Int. I. Pept. Protein
Res., 10:172-75.
1979
With Stanford Moore. In: 75 Years of Chromatography A Historical
Dialogue, ed. L. S. Ettre and A. Zlatkis, pp. 297-308. Amster-
dam: Elsevier.
OCR for page 441
Representative terms from entire chapter:
amino acids