Terpolymerization kinetics of amino acid N-carboxy anhydrides

Based on their versatility with respect to amino acid type and sequence, polypeptides have become attractive for a number of biological applications such as drug delivery, biomineralization, and drugs. N-carboxy anhydride (NCA) polymerization is a convenient way to rapidly prepare high-molecular weight polypeptides with good control over molecular weight and polydispersity. However, the kinetics of the incorporation of NCA monomers into copolypeptides during random copolymerization are poorly understood. Here, kinetic data is presented that allows insight into the NCA polymerization of a terpolymer composed of three commercially relevant amino acids, namely, glutamic acid, lysine, and tyrosine. Furthermore, kinetic data and copolymerization parameters from the copolymerization of binary mixtures of these three amino acid NCAs is used to make predictions of the terpolymer composition. This study provides access to the information necessary to prepare functional copolypeptides with better-defined sequence architecture that will be essential for the future development of polypeptide-based materials.