Strategies in the racemization-free synthesis of polytripeptide models of collagen.

Abstract

Synthesis of racemization-free sequential polypeptides is a major challenge to the peptide chemist. The loss of optical integrity at a single residue can drastically alter the properties of the polymer. We have investigated racemization in the synthesis of polytripeptide models of collagen. The conformational features of collagen are determined by a large imino content and the presence of Gly in every third position. Thus polymers of tripeptides containing Pro and Gly with an asymmetric residue A permit evaluation of the contribution of A to collagen conformation. in the synthesis of such polymers, the position of Pro in the tripeptide is of importance because of its variable reactivity at the N or C terminal residue. N-terminal Pro is more reactive but also sterically hinders polycondensation. Terminal Pro also participates in undesirable side reactions such as formation of urea or diketopiperazine derivatives and cyclization. Cyclization can be avoided by using concentrated solutions of monomer. Racemization occurs during the synthesis of OCl5Ph or ONp esters but not in the synthesis of ONSu esters. This, however, does not guarantee formation of optically pure products. Best results are obtained with ONSu esters and limited use of base during polymerization. Polymerization appears to be stereoselective since the largest molecular weight polymers are purest, smallest molecular weight products highly racemized.