Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences Building, Corvallis, OR 97331-7305, USA; GCE4All Research Center, Oregon State University, 2011 Agricultural and Life Sciences, Corvallis, OR 97331-7305, USA.
Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences Building, Corvallis, OR 97331-7305, USA; GCE4All Research Center, Oregon State University, 2011 Agricultural and Life Sciences, Corvallis, OR 97331-7305, USA.
Cell Chem Biol. 2023 Apr 20;30(4):343-361. doi: 10.1016/j.chembiol.2023.03.004. Epub 2023 Mar 27.
The ability to selectively modify proteins at two or more defined locations opens new avenues for manipulating, engineering, and studying living systems. As a chemical biology tool for the site-specific encoding of non-canonical amino acids into proteins in vivo, genetic code expansion (GCE) represents a powerful tool to achieve such modifications with minimal disruption to structure and function through a two-step "dual encoding and labeling" (DEAL) process. In this review, we summarize the state of the field of DEAL using GCE. In doing so, we describe the basic principles of GCE-based DEAL, catalog compatible encoding systems and reactions, explore demonstrated and potential applications, highlight emerging paradigms in DEAL methodologies, and propose novel solutions to current limitations.
选择性地在两个或更多定义的位置修饰蛋白质的能力为操纵、工程和研究生命系统开辟了新途径。作为一种用于在体内将非规范氨基酸特异性编码到蛋白质中的化学生物学工具,遗传密码扩展(GCE)代表了一种强大的工具,可以通过两步“双重编码和标记”(DEAL)过程,以最小的结构和功能干扰实现这种修饰。在本综述中,我们总结了使用 GCE 的 DEAL 领域的现状。在这样做的过程中,我们描述了基于 GCE 的 DEAL 的基本原理,列出了兼容的编码系统和反应,探索了已证明的和潜在的应用,突出了 DEAL 方法学中的新兴范例,并提出了当前限制的新解决方案。