Polypeptides have broad applications and can be prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Conventional initiators, such as primary amines, give slow NCA polymerization, which requires multiple days to reach completion and can result in substantial side reactions, especially for very reactive NCAs. Moreover, current NCA polymerizations are very sensitive to moisture and must typically be conducted in a glove box. Here we show that lithium hexamethyldisilazide (LiHMDS) initiates an extremely rapid NCA polymerization process that is completed within minutes or hours and can be conducted in an open vessel. Polypeptides with variable chain length (DP = 20-1294) and narrow molecular weight distribution (Mw/Mn = 1.08-1.28) were readily prepared with this approach. Mechanistic studies support an anionic ring opening polymerization mechanism. This living NCA polymerization method allowed rapid synthesis of polypeptide libraries for high-throughput functional screening.

中文翻译：

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六甲基二硅叠氮化锂引发了α-氨基酸N-羧基酸酐的超快开环聚合反应。

多肽具有广泛的用途，可以通过α-氨基酸N-羧基酸酐（NCA）的开环聚合反应制备。常规的引发剂，例如伯胺，会导致NCA聚合反应缓慢，这需要几天的时间才能完成，并且可能导致大量的副反应，尤其是对于反应性很强的NCA。而且，当前的NCA聚合对水分非常敏感，并且通常必须在手套箱中进行。在这里，我们表明六甲基二硅叠氮化锂（LiHMDS）引发了非常快速的NCA聚合过程，该过程可在数分钟或数小时内完成，并且可以在开放式容器中进行。用这种方法可以很容易地制备出具有可变链长（DP = 20-1294）和窄分子量分布（Mw / Mn = 1.08-1.28）的多肽。机理研究支持阴离子开环聚合机理。这种有效的NCA聚合方法可快速合成多肽库，以进行高通量功能筛选。