Protease-catalyzed regioselective polymerization and copolymerization of glutamic acid diethyl ester

Protease-catalyzed polymerization and copolymerization of L-glutamic acid diethyl ester hydrochloride (1) have been performed in a buffer of high concentration. Papain and bromelain showed high catalytic activity toward the polymerization. H-H COSY NMR analysis of the product showed the exclusive formation of poly(alpha-peptide), which was further confirmed by comparison with NMR spectra of poly(alpha-methyl gamma-L-glutamate). The papain-catalyzed polymerization of gamma-methyl L-glutamate did not occur under the similar reaction conditions, supporting the regioselective production of the polymer having an alpha-peptide linkage from 1. The effects of the reaction parameters have been systematically investigated. The copolymerization of 1 with various amino acid esters took place by the papain catalyst to give peptide copolymers.