Polypeptides have been widely utilized in the fields of biomaterials and biomedicine. Ever since N-carboxyanhydride (NCA) was reported by Hermann Leuchs in 1906, ring-opening polymerization of NCAs has been extensively used to prepare polypeptides. Despite continuous innovations, it is still challenging to synthesize polypeptides in high molecular weight efficiently. To address this challenge, we developed KHMDS/NaHMDS initiated fast NCA polymerization that is also moisture tolerant, open-flask amenable and terminal tunable. This NCA polymerization was able to proceed in most common solvents and meet the solubility requirement of variable NCA monomers and corresponding polypeptides. KHMDS can initiate γ-benzyl-L-glutamate-N-carboxyanhydride (BLG NCA) polymerization in a reaction rate 92 times faster than does hexylamine and 80 times faster than does triethylamine. This NCA polymerization also demonstrated easy and fast synthesis of gram-scale long chain polypeptides in an open flask.

多肽已被广泛用于生物材料和生物医学领域。自从1906年Hermann Leuchs报道N-羧基酐（NCA）以来，NCA的开环聚合已广泛用于制备多肽。尽管进行了持续的创新，但仍然难以有效地合成高分子量的多肽。为了应对这一挑战，我们开发了KHMDS / NaHMDS引发的快速NCA聚合反应，该聚合反应还具有耐湿性，开瓶适应性和终端可调性。该NCA聚合反应能够在大多数普通溶剂中进行，并满足可变NCA单体和相应多肽对溶解度的要求。KHMDS可以引发γ-苄基-L-谷氨酸-N-羧基酸酐（BLG NCA）的聚合反应速率比己胺快92倍，比三乙胺快80倍。该NCA聚合反应还证明了在敞口烧瓶中容易快速地合成出克级的长链多肽。