Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Department of Chemistry and Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269, USA.
Nat Chem. 2017 Jul;9(7):614-622. doi: 10.1038/nchem.2712. Epub 2017 Feb 6.
Catalysis observed in enzymatic processes and protein polymerizations often relies on the use of supramolecular interactions and the organization of functional elements in order to gain control over the spatial and temporal elements of fundamental cellular processes. Harnessing these cooperative interactions to catalyse reactions in synthetic systems, however, remains challenging due to the difficulty in creating structurally controlled macromolecules. Here, we report a polypeptide-based macromolecule with spatially organized α-helices that can catalyse its own formation. The system consists of a linear polymeric scaffold containing a high density of initiating groups from which polypeptides are grown, forming a brush polymer. The folding of polypeptide side chains into α-helices dramatically enhances the polymerization rate due to cooperative interactions of macrodipoles between neighbouring α-helices. The parameters that affect the rate are elucidated by a two-stage kinetic model using principles from nucleation-controlled protein polymerizations; the key difference being the irreversible nature of this polymerization.
在酶促过程和蛋白质聚合中观察到的催化作用通常依赖于超分子相互作用的利用和功能元件的组织，以获得对基本细胞过程的时空元素的控制。然而，由于难以创建结构受控的大分子，因此利用这些协同相互作用在合成系统中催化反应仍然具有挑战性。在这里，我们报告了一种基于多肽的大分子，其具有空间组织的α-螺旋，可催化其自身的形成。该系统由线性聚合物支架组成，其中包含高密度的起始基团，从这些起始基团生长多肽，形成刷状聚合物。由于相邻α-螺旋之间的宏观偶极子的协同相互作用，多肽侧链折叠成α-螺旋极大地提高了聚合速率。使用来自成核控制的蛋白质聚合的原理通过两阶段动力学模型阐明了影响速率的参数；关键区别在于这种聚合的不可逆性质。
