Triphenylphosphine-Initiated Ring-Opening Polymerization for α-Helical Polypeptides and Application in Constructing Artificial Ion Channels.

Abstract

In this study, we have screened out an effective triphenylphosphine-derived initiator (2-TMOPP) for efficient ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCA ROP) and demonstrated the potential of the prepared helical polypeptide as an efficient ion channel. By optimizing polymerization conditions, 2-TMOPP exhibited precise control over the molecular weight and polydispersity index for the prepared polypeptides, the universality for different NCA monomers, and the ability to form α-helical secondary structures. By further incorporating ion binding groups and regulating the molecular length, α-helical polypeptide PLCE was capable of inserting into lipid bilayers and possessing the function of ion transport (H⁺/K⁺ antiport) via a channel mechanism (EC₅₀ = 12.75 ± 1.58 μg mL^-1). PLCE also showed anticancer activity toward HeLa cells, with an IC₅₀ value of approximately 69.67 ± 1.20 μg mL^-1 after 20 h coculture, showing the possibility for future practical application in biomedical fields.