Department of Materials Science and Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
ACS Nano. 2020 Mar 24;14(3):3344-3352. doi: 10.1021/acsnano.9b09070. Epub 2020 Feb 20.
Understanding the intermediates or transition states in organic reactions has made it possible to develop theories and to synthesize important compounds. In contrast to organic reaction intermediates and even protein folding intermediates, the intermediates of peptide/protein self-assembly are not very well understood. Here we report that the self-assembly kinetics of linear heterochiral peptides are significantly slower than those of the corresponding homochiral peptides, which enables direct microscopic observation of assembly intermediates. By designing racemic or asymmetric heterochiral peptides, we were able to discover unusual mixed helical (-helix) and overtwisted intermediates. The convergence of equilibrium morphology between the homochiral and heterochiral peptides enables us to reasonably deduce the unobservable intermediates of rapidly assembling homochiral peptides. By utilizing the discovered information about the assembly intermediates, we were able to develop a functional NMR alignment medium that enables the measurement of residual dipolar couplings (RDCs) in a time-dependent manner. Although much less studied than their cyclic counterparts, the linear form of heterochiral peptides provides a means of obtaining a more in-depth understanding of the self-assembly pathway and of developing sophisticated bottom-up materials.
理解有机反应中的中间体或过渡态使得开发理论和合成重要化合物成为可能。与有机反应中间体甚至蛋白质折叠中间体相比，肽/蛋白质自组装的中间体还不是很清楚。在这里，我们报告说，线性杂手性肽的自组装动力学明显慢于相应的同手性肽，这使得可以直接观察到组装中间体。通过设计外消旋或不对称杂手性肽，我们能够发现不寻常的混合螺旋（-螺旋）和过度扭曲中间体。同手性和杂手性肽之间平衡形态的收敛使我们能够合理推断出快速组装同手性肽的不可观察中间体。通过利用关于组装中间体的发现信息，我们能够开发出一种功能 NMR 对准介质，该介质能够以时间依赖的方式测量残余偶极耦合（RDC）。尽管它们比环状对应物研究得少，但杂手性肽的线性形式提供了一种更深入了解自组装途径和开发复杂自下而上材料的手段。
