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Science 18 November 1988:
Vol. 242. no. 4881, pp. 1038 - 1040
DOI: 10.1126/science.3194752

Articles

Science, Vol 242, Issue 4881, 1038-1040
Copyright © 1988 by American Association for the Advancement of Science


articles

Introduction of nucleophiles and spectroscopic probes into antibody combining sites

SJ Pollack, GR Nakayama, and PG Schultz

Department of Chemistry, University of California, Berkeley 94720.

A general chemical strategy has been developed whereby antibody combining sites can be selectively derivatized with natural or synthetic molecules, such as catalytic groups, drugs, metals, or reporter molecules. Cleavable affinity labels were used to selectively introduce a thiol into the combining site of the immunoglobulin A MOPC 315. This thiol acted both as a nucleophile to accelerate ester thiolysis 60,000-fold and as a handle for selectively derivatizing the antibody with additional functional groups. For example, derivatization of the antibody with a fluorophore made possible a direct spectroscopic assay of antibody-ligand complexation. This chemistry should not only extend our ability to exploit antibody specificity in chemical catalysis, diagnostics, and therapeutics, but may also prove generally applicable to the functional modification of other proteins for which detailed structural information is unavailable.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Selection of optical biosensors from chemisynthetic antibody libraries.
L. Jespers, T. P. Bonnert, and G. Winter (2004)
Protein Eng. Des. Sel. 17, 709-713
   Abstract »    Full Text »    PDF »
At the crossroads of chemistry and immunology: catalytic antibodies.
R. Lerner, S. Benkovic, and P. Schultz (1991)
Science 252, 659-667
   Abstract »    PDF »
Generation of a catalytic antibody by site-directed mutagenesis.
E Baldwin and P. Schultz (1989)
Science 245, 1104-1107
   Abstract »    PDF »
Sequence-specific peptide cleavage catalyzed by an antibody.
B. Iverson and R. Lerner (1989)
Science 243, 1184-1188
   Abstract »    PDF »
A New Effector Mechanism for Antibodies: Catalytic Cleavage of Peptide Bonds.
S. Paul (1989)
Cold Spring Harb Symp Quant Biol 54, 283-286
   Abstract »    PDF »



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Science. ISSN 0036-8075 (print), 1095-9203 (online)