Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Department of Chemistry, University of Connecticut, Storrs, CT 06269.
Proc Natl Acad Sci U S A. 2019 May 28;116(22):10658-10663. doi: 10.1073/pnas.1901442116. Epub 2019 May 14.
Ribozymes synthesize proteins in a highly regulated local environment to minimize side reactions caused by various competing species. In contrast, it is challenging to prepare synthetic polypeptides from the polymerization of -carboxyanhydrides (NCAs) in the presence of water and impurities, which induce monomer degradations and chain terminations, respectively. Inspired by natural protein synthesis, we herein report the preparation of well-defined polypeptides in the presence of competing species, by using a water/dichloromethane biphasic system with macroinitiators anchored at the interface. The impurities are extracted into the aqueous phase in situ, and the localized macroinitiators allow for NCA polymerization at a rate which outpaces water-induced side reactions. Our polymerization strategy streamlines the process from amino acids toward high molecular weight polypeptides with low dispersity by circumventing the tedious NCA purification and the demands for air-free conditions, enabling low-cost, large-scale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials.
核酶在高度调控的局部环境中合成蛋白质，以最大限度地减少各种竞争物种引起的副反应。相比之下，在水和杂质存在的情况下，通过聚合β-内酰胺（NCAs）来制备合成多肽具有挑战性，因为这分别会导致单体降解和链终止。受天然蛋白质合成的启发，我们在此报告了在存在竞争物种的情况下，通过使用在界面上锚定大分子引发剂的水/二氯甲烷两相体系，来制备结构明确的多肽。杂质原位被提取到水相中，局部的大分子引发剂允许 NCA 聚合的速率超过水诱导的副反应。我们的聚合策略通过避免繁琐的 NCA 纯化和对无氧条件的需求，简化了从氨基酸向高分子量多肽的过程，具有低成本、大规模生产多肽的潜力，可能改变基于多肽的生物材料的范式。
