Soluble, Clickable Polypeptides from Azide-Containing N‑Carboxyanhydride Monomers

We report a method for the synthesis of soluble, well-defined, azide-functionalized polypeptides via living polymerization of new azide-containing amino acid N-carboxyanhydride (NCA) monomers. Homo and diblock azidopolypeptides were prepared with controlled segment lengths using (PMe3)4Co initiator and were subsequently modified by reaction with functional alkyne reagents. The azide groups were found to be quantitatively converted to the corresponding triazole derivatives, and the functionalized polymers were obtained in high yield. This methodology provides a facile and straightforward method for preparation of functional and side-chain reactive, high molecular weight polypeptides.