英国曼彻斯特大学David A. Leigh团队报道了两台人工分子机器并行操作的序列选择性十肽合成。相关研究成果于2021年3月25日发表在国际知名学术期刊《美国化学会杂志》。

研究人员人员报告了通过两个基于轮烷的分子机器的并行操作的十肽的制备。合成过程分为四个阶段：（1）在同一反应容器中同时操作两个分子肽合成器；（2）短低聚物中间体的选择性残基活化；（3）连接；（4）产物释放。

机器设计的主要特点包括：（a）选择性地将巯基脯氨酸构建基块转化为半胱氨酸（一旦它被一个分子机器并入六肽中间体）；（b）大环肽联氨键（作为第二台机器的一部分）以区分中间体并实现其功能定向连接；以及（c）在一台机器的组装模块中加入谷氨酸残基，以使最终产品能够释放，同时从产品中移除组装机械的一部分。

这两种分子机器参与的产物的合成超出了单个小分子机器的能力，其方式让人联想到生物学中蛋白质的连接和翻译后修饰。

附：英文原文

Title: Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines

Author: Javier Echavarren, Malcolm A. Y. Gall, Adrian Haertsch, David A. Leigh, Justin T. J. Spence, Daniel J. Tetlow, Chong Tian

Issue&Volume: March 25, 2021

Abstract: We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include the following: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability of individual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology.

DOI: 10.1021/jacs.1c01234

Source: https://pubs.acs.org/doi/10.1021/jacs.1c01234