Synthesis of poly-α/β-peptides with tunable sequence via the copolymerization on N-carboxyanhydride and N-thiocarboxyanhydride

The fascinating functions of proteins and peptides in biological systems have attracted intense interest to explore their mimics using polymers, including polypeptides synthesized from polymerization. The folding, structures and functions of proteins and polypeptides are largely dependent on their sequence. However, sequence-tunable polymerization for polypeptide synthesis is a long-lasting challenge. The application of polypeptides is also greatly hindered by their susceptibility to enzymatic degradation. Although poly-α/β-peptide has proven to be an effective strategy to address the stability issue, the synthesis of poly-α/β-peptide from polymerization is not available yet. Hereby, we demonstrate a living and controlled copolymerization on α-NCA and β-NTA to prepare sequence-tunable poly-α/β-peptides. This polymerization strategy shows a prominent solvent-driven characteristic, providing random-like copolymers of poly-α/β-peptides in THF and block-like copolymers of poly-α/β-peptides in a mixed solvent of CHCl(3)/H(2)O (95/5, v/v), and opens new avenues for sequence-tunable polymerization and enables facile synthesis of proteolysis tunable poly-α/β-peptides for diverse applications.