Antibody catalysis of peptide bond formation.
An antibody generated against a neutral phosphonate diester transition-state (TS not equal to) 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.
Jacobsen
J R
JR
Department of Chemistry, University of California, Berkeley 94720.
Schultz
P G
PG
D000409:Alanine; D000906:Antibodies; D001386:Azides; D002384:Catalysis; D006241:Haptens; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010453:Peptide Synthases; D010455:Peptides / Q000138:chemical synthesis*; D010649:Phenylalanine; D012710:Serum Albumin, Bovine; D013237:Stereoisomerism; D013379:Substrate Specificity
D000906:Antibodies; D001386:Azides; D006241:Haptens; D007202:Indicators and Reagents; D010455:Peptides; D012710:Serum Albumin, Bovine; D010649:Phenylalanine; D010453:Peptide Synthases; D000409:Alanine