PEPTIDE-SYNTHESIS CATALYZED BY AN ANTIBODY CONTAINING A BINDING-SITE FOR VARIABLE AMINO-ACIDS

Monoclonal antibodies, induced with a phosphonate diester hapten, cata lyzed the coupling of p-nitrophenyl esters of N-acetyl valine, leucine , and phenylalanine with tryptophan amide to form the corresponding di peptides. All possible stereoisomeric combinations of the ester and am ide substrates were coupled at comparable rates. The antibodies did no t catalyze the hydrolysis of the dipeptide product nor hydrolysis or r acemization of the activated esters. The yields of the dipeptides rang ed from 44 to 94 percent. The antibodies were capable of multiple turn overs at rates that exceeded the rate of spontaneous ester hydrolysis. This achievement suggests routes toward creating a small number of an tibody catalysts for polypeptide syntheses.