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Isolation and Characterization of Antibodies
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Isolation and Characterization of Antibodies: the Work of Michael Sela Isolation and Characterization of Active Fragments Obtained by Cleavage of Immu- noglobulin G with Cyanogen Bromide (Cahnmann, H. J., Arnon, R., and Sela, M. (1966) J. Biol. Chem. 241, 3247–3255) Recovery of Specific Activity upon Reoxidation of Completely Reduced Polyalanyl Rabbit Antibody (Freedman, M. H., and Sela, M. (1966) J. Biol. Chem. 241, 5225–5232) Michael Se la was born in Tomasz o ´w Ma- zo wi ecki , Poland, in 1924. He grew up in the cour tyard of a textil e fac tory and intended to study fibers but ended up researching macromol- ecules when, as a graduate student, he joined the laborator y of Eph rai m Kat chalski at the Wei z- mann Institute of Science. Katchalski was explor- ing the use of polyamino acids as protein models, and Sela became involved in the synthesis of poly- L-tyro sine, poly-3 ,5-dii odoty rosin e, and poly- p- amino-L-phenylalanine. Later on, he aided in the synt hesis of polyt rypto phan and polyc ycloh exyl- alanine. For his dissertation, Sela looked at the azo der ivatives of some aromatic pol y- -amino acids (1). After receiving his Ph.D., Sela joined the labo- ratory of Journal of Biological Chemistry (JBC) Classic author Christian Anfinsen (2) at the Na- tional Institutes of Health in Bethesda. During this postdoctoral fellowship, Sela looked at the selective cleavage of protein chains by trypsin at arginine residues after lysine residues were re- versibly blocked by carbobenzoxy groups (3). He also explored reductive cleavage of ribonuclease, followed by blocking of the sulfhydryl groups with iodoa cetic acid (4). Whil e doin g these experiments, Sela and Anfinsen decided to leave part of the reduced ribonuclease unblocked to see if it could reoxidize properly and regain its enzy- matic activity. The enzyme showed a total recovery of activity (5), demonstrating that the three- di mensional struct ur e of a pr otei n is the result of its amino acid sequence. Anfin sen went on to receive the 1972 Nobel Prize in chemistry for his research on the connection between the amino acid sequence and the biolog ically active conformat ion of ribon uclease. Sela returned to the Weizmann Institute in 1957. He became interested in immunogenicity and antigenic specificity after reading Karl Landsteiner’s book, “The Specificity of Serological Reactions,” and learning that gelatin probably is not antigenic because it contains no tyrosine. Intrigued, Sela explored the possibility of increasing the antigenicity of gelatin by attaching tyros ine pepti des and showe d that limit ed tyros ylati on enhan ced immu nogen icity without Michael Sela THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 285, No. 39, Issue of September 24, p. e12, 2010 © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A. Classics A PAPER IN A SERIES REPRINTED TO CELEBRATE THE CENTENARY OF THE JBC IN 2005 JBC Centennial 1905–2005 100 Years of Biochemistry and Molecular Biology This paper is available on line at http://www.jbc.org e12 b y g u e s t , o F e b r u a r y 1 1 , 2 0 1 1 w w w . j b c o r D o w n l o a d e d f r o m
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Transcript of Isolation and Characterization of Antibodies
8/7/2019 Isolation and Characterization of Antibodies
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Isolation and Characterization of Antibodies: the Work of Michael Sela
Isolation and Characterization of Active Fragments Obtained by Cleavage of Immu-noglobulin G with Cyanogen Bromide(Cahnmann, H. J., Arnon, R., and Sela, M. (1966) J. Biol. Chem. 241, 3247–3255)
Recovery of Specific Activity upon Reoxidation of Completely Reduced Polyalanyl
Rabbit Antibody
(Freedman, M. H., and Sela, M. (1966)J. Biol. Chem.
241, 5225–5232)Michael Sela was born in Tomaszow Ma-
zowiecki, Poland, in 1924. He grew up in the
courtyard of a textile factory and intended tostudy fibers but ended up researching macromol-ecules when, as a graduate student, he joined thelaboratory of Ephraim Katchalski at the Weiz-mann Institute of Science. Katchalski was explor-ing the use of polyamino acids as protein models,and Sela became involved in the synthesis of poly-L-tyrosine, poly-3,5-diiodotyrosine, and poly-p-amino-L-phenylalanine. Later on, he aided in the
synthesis of polytryptophan and polycyclohexyl-alanine. For his dissertation, Sela looked at theazo derivatives of some aromatic poly--aminoacids (1).
After receiving his Ph.D., Sela joined the labo-ratory of Journal of Biological Chemistry (JBC)Classic author Christian Anfinsen (2) at the Na-tional Institutes of Health in Bethesda. Duringthis postdoctoral fellowship, Sela looked at the
selective cleavage of protein chains by trypsin atarginine residues after lysine residues were re-versibly blocked by carbobenzoxy groups (3). Healso explored reductive cleavage of ribonuclease,followed by blocking of the sulfhydryl groups with
iodoacetic acid (4). While doing these experiments, Sela and Anfinsen decided to leave part of
the reduced ribonuclease unblocked to see if it could reoxidize properly and regain its enzy-
matic activity. The enzyme showed a total recovery of activity (5), demonstrating that the
three-dimensional structure of a protein is the result of its amino acid sequence. Anfinsen went
on to receive the 1972 Nobel Prize in chemistry for his research on the connection between the
amino acid sequence and the biologically active conformation of ribonuclease.
Sela returned to the Weizmann Institute in 1957. He became interested in immunogenicity
and antigenic specificity after reading Karl Landsteiner’s book, “The Specificity of Serological
Reactions,” and learning that gelatin probably is not antigenic because it contains no tyrosine.
Intrigued, Sela explored the possibility of increasing the antigenicity of gelatin by attaching
tyrosine peptides and showed that limited tyrosylation enhanced immunogenicity without
Michael Sela
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 285, No. 39, Issue of September 24, p. e12, 2010© 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A.
ClassicsA PAPER IN A SERIES REPRINTED TO CELEBRATE THE CENTENARY OF THE JBC IN 2005
JBC Centennial1905–2005
100 Years of Biochemistry and Molecular Biology
This paper is available on line at http://www.jbc.orge12
8/7/2019 Isolation and Characterization of Antibodies
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8/7/2019 Isolation and Characterization of Antibodies
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