Enzyme-mimetic self-catalyzed polymerization of polypeptide helices
Enzyme-mimetic self-catalyzed polymerization of polypeptide helices
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DOI：
10.1038/s41467-019-13502-w
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发表时间：
2019-11-29
影响因子：
16.6
通讯作者：
Cheng, Jianjun
中科院分区：
文献类型：
--
作者：
Song, Ziyuan;Fu, Hailin;Cheng, Jianjun
酶为底物结合和随后的加速反应提供最佳的三维结构。然而，这种依赖折叠的催化行为很少在结构复杂性降低的情况下从机理上进行探索。在这里，我们证明了α-螺旋，一个简单得多的结构基序，可以通过N-羧酸酐(NCA)在二氯甲烷中的自催化聚合来促进自身的生长。α-螺旋多肽的N端与NCA之间的可逆结合促进了随后的开环反应的速度加快。通过考虑螺旋链与单体之间的结合和反应，提出了一个两阶段的Michaelis-Menten型动力学模型，并成功地用于预测聚合物的相对分子质量和相对分子质量分布。这项工作阐明了螺旋诱导的模拟酶催化的机理，强调了溶剂选择在发现新的反应类型中的重要性，并为利用自加速开环聚合快速生产定义良好的合成多肽提供了一条途径。
Enzymes provide optimal three-dimensional structures for substrate binding and the subsequent accelerated reaction. Such folding-dependent catalytic behaviors, however, are seldom mechanistically explored with reduced structural complexity. Here, we demonstrate that the alpha-helix, a much simpler structural motif of enzyme, can facilitate its own growth through the self-catalyzed polymerization of N-carboxyanhydride (NCA) in dichloromethane. The reversible binding between the N terminus of alpha-helical polypeptides and NCAs promotes rate acceleration of the subsequent ring-opening reaction. A two-stage, Michaelis-Menten-type kinetic model is proposed by considering the binding and reaction between the propagating helical chains and the monomers, and is successfully utilized to predict the molecular weights and molecular-weight distributions of the resulting polymers. This work elucidates the mechanism of helix-induced, enzyme-mimetic catalysis, emphasizes the importance of solvent choice in the discovery of new reaction type, and provides a route for rapid production of well-defined synthetic polypeptides by taking advantage of self-accelerated ring-opening polymerizations.