Versatile fully-substituted triazole-functionalized polypeptides with a stable α-helical conformation for gene delivery

A library of polypeptides bearing fully-substituted triazoles (FT) was developed via a Cu-catalyzed multicomponent reaction (MCR). Such an MCR allowed the efficient construction of polypeptide platforms. The introduction of FT avoided the undesired hydrogen bonding compared to traditional triazoles and stabilized the α-helix in a broad pH range. Their gene delivery performance in serum also demonstrates their potential in biological applications.