Antibody Catalysis of Peptide Bond Formation

An antibody generated against a neutral phosphonate diester transition-state (TS‡) analog catalyzes the formation of an amide bond between a phenylalanyl amino group and an acyl azide derived from L-alanine. The antibody is selective for L- vs. D-alanine and does not catalyze the hydrolysis of the a...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-06, Vol.91 (13), p.5888-5892
Main Authors: Jacobsen, John R., Schultz, Peter G.
Format: Article
Language:English
Subjects:
Alanine
Amides
Amines
Amino acids
Antibodies
Azides
Biochemistry
Catalysis
Chlorides
Esters
Haptens
Indicators and Reagents
Kinetics
Magnetic Resonance Spectroscopy
Mass spectra
Mass Spectrometry
Peptide Synthases
Peptides - chemical synthesis
Phenylalanine
Room temperature
Serum Albumin, Bovine
Sodium
Stereoisomerism
Substrate Specificity
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Description
Summary:An antibody generated against a neutral phosphonate diester transition-state (TS‡) analog catalyzes the formation of an amide bond between a phenylalanyl amino group and an acyl azide derived from L-alanine. The antibody is selective for L- vs. D-alanine and does not catalyze the hydrolysis of the acyl azide to an appreciable degree. A rate acceleration of 10,000-fold relative to the uncatalyzed reaction is observed. The antibody may achieve its catalytic efficiency both by acting as an entropy trap and by stabilizing the deprotonated form of the amine nucleophile. These experiments constitute a first step toward a general strategy for the generation of sequence-specific peptide ligases.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.13.5888