Facile terminal functionalization of peptides by protease-catalyzed chemoenzymatic polymerization toward synthesis of polymeric architectures consisting of peptides

Polypeptides are used as building blocks that assemble into polymeric hierarchical architectures with various functionalities based on their amino acid sequences. Chemoenzymatic polymerization using a protease as a catalyst allows us to synthesize peptides with various primary structures in an environmentally benign way. In this work, we performed papain-catalyzed polymerization in the presence of terminal-modifying agents to synthesize peptides modified with a functional group at their N-terminus. Various peptides with a reactive acrylamide group at the N-terminus were synthesized in a one-pot chemoenzymatic reaction with the side groups of the amino acid residues left intact. Acrylamide-modified poly(L-alanine) was used as a macromonomer in a radical copolymerization with N-isopropylacrylamide to give a graft copolymer consisting of poly(L-alanine) side chains.