Synthesis of Block Copolypeptides by Click Chemistry

Abstract

Abstract A novel synthetic methodology to diblock copolypeptides was developed by ring‐opening polymerization (ROP) of N ‐carboxyanhydrides (NCAs) from α ‐ ω ‐functionalized initiators combined with the Huisgen 1,3 dipolar cycloaddition (click chemistry). Poly( γ ‐benzyl‐ L ‐glutamate) (PBLGlu) and poly(trifluoroacetyl‐ L ‐Lysine) (PTFALys) containing either an azide or an alkyne functional group in α ‐position were first synthesized by ROP of the corresponding NCA at room temperature in DMF as a solvent, using appropriate ω ‐amino‐containing α ‐alkyne and α ‐azido difunctional initiators. The copper( I )‐catalyzed coupling reactions of α ‐azido‐PBLGlu with the α ‐alkyne‐PTFALys, on the one hand, and of the α ‐alkyne‐PBLGlu with the α ‐azido‐PTFALys, on the other hand were suitably accomplished in DMF. This afforded the targeted PBLGlu‐ b ‐PTFALys diblock copolypeptides possessing a triazole group in between the two blocks, as evidenced by SEC, IR, and NMR analysis. Block copolypeptides could be successfully purified by selective extraction with chloroform. magnified image