Carboxypeptidase Y catalyzed peptide synthesis using amino acid alkyl esters as amine components

Abstract

Carboxypeptidase Y catalyzed transacylation reactions between N-protected amino acid methyl esters or peptide methyl esters as initial acyl components and methyl, ethyl, isopropyl or tert.-butyl esters of different α-amino acids as amine components are described. The yield of peptide bond formation and the extent of oligomerization of the amine components both depend on the nature of their side chain as well as on the nature of their alkyl ester group. Thus, the methyl esters of all hydrophobic amino acids that were tested oligomerized to various extents (in total product yields ranging from 60–90%). On the other hand, the methyl esters of the hydrophilic amino acids did not oligomerize, and were incorporated in yields ranging from 25–50 %. Increasing the size of the ester group from methyl, to ethyl, to propyl etc. resulted in a drastic decrease of the degree of oligomerization and — with the exception of glycine — led to reduced coupling yields.