Determination of copolymerisation characteristics in the N-​carboxy anhydride polymerization of two amino acids

Polypeptides are increasingly used as components for biomedical materials. Based on the variety of functional groups and the inherent biocompatibility presented by natural amino acids, the potential functionality offered by polypeptides is considerable and methods based on NCA monomers have been developed to readily access polypeptides of high mol. wt. synthetically. Despite some isolated examples of the functionality of random synthetic copolypeptides (e.g., the drug glatiramer acetate)¿, applications of synthetic copolypeptides are thus far mainly restricted to block-¿polymers because of poor control over the random amino acid NCA polymn. This restricted use of random copolypeptides is in large parts due to the inability to monitor the kinetics of the individual monomers, an aspect crucial to understanding and controlling the copolymns. Here, a method is presented that allows monitoring of the consumption of two model NCAs, Glu(Bzl)¿-¿NCA and Lys(Z)¿-¿NCA. This procedure makes kinetic data of the monomer consumption in an NCA copolymn. accessible for the first time and shows how the different reactivities of the two NCAs in binary mixts. of various monomer ratios affect the compn. of the copolymer over time.