Proximity-Induced Cooperative Polymerization in "hinged" Helical Polypeptides

Cooperative interactions and transitions are among the most important strategies utilized by biological systems to regulate a variety of physical and chemical processes. We report herein an auto-accelerated, rapid cooperative polymerization of N-carboxyanhydrides (NCAs) with initiators structurally as simple as linear aliphatic diamines for the synthesis of polypeptides. The polymerization initiated by diamines proceeds via the formation of "hinged" polypeptides, which are two blocks of helical chains connected head-to-head by the diamine molecules in the polymerization solution. The reactions follow a two-stage, cooperative polymerization kinetic; the cooperative interactions between the macrodipoles of the two hinged helical polypeptides dramatically accelerate the polymerization. Compared to the NCA polymerization initiated by the hexylamine (CH₃(CH₂)₅NH₂), the chain propagation rate of the NCA polymerization is increased by more than 600 times when initiated by its diamine analogue (1,6-diaminohexane, NH₂(CH₂)₆NH₂). This proximity-induced cooperative polymerization showcases the single helix as a remarkable cooperativity-enabling motif in synthetic chemistry.