Chen Guo-Qiang, Xu Ying, Shen Shao-Ming, Zhang Jian
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Natl Sci Rev. 2019 Nov;6(6):1111-1127. doi: 10.1093/nsr/nwy124. Epub 2018 Nov 1.
Chemical biology has been attracting a lot of attention because of the key roles of chemical methods and techniques in helping to decipher and manipulate biological systems. Although chemical biology encompasses a broad field, this review will focus on chemical biology aimed at using exogenous chemical probes to interrogate, modify and manipulate biological processes, at the cellular and organismal levels, in a highly controlled and dynamic manner. In this area, many advances have been achieved for cancer biology and therapeutics, from target identification and validation based on active anticancer compounds (forward approaches) to discoveries of anticancer molecules based on some important targets including protein-protein interaction (reverse approaches). Herein we attempt to summarize some recent progresses mainly from China through applying chemical biology approaches to explore molecular mechanisms of carcinogenesis. Additionally, we also outline several new strategies for chemistry to probe cellular activities such as proximity-dependent labeling methods for identifying protein-protein interactions, genetically encoded sensors, and light activating or repressing gene expression system.
化学生物学因其化学方法和技术在帮助解密和操纵生物系统中所起的关键作用而备受关注。尽管化学生物学涵盖的领域很广,但本综述将聚焦于利用外源性化学探针在细胞和生物体水平上以高度可控和动态的方式询问、修饰和操纵生物过程的化学生物学。在这一领域,癌症生物学和治疗学已经取得了许多进展,从基于活性抗癌化合物的靶点识别和验证(正向方法)到基于包括蛋白质-蛋白质相互作用在内的一些重要靶点发现抗癌分子(反向方法)。在此,我们试图通过应用化学生物学方法来探索致癌分子机制,主要总结来自中国的一些最新进展。此外,我们还概述了化学探测细胞活性的几种新策略,如用于识别蛋白质-蛋白质相互作用的邻近依赖性标记方法、基因编码传感器以及光激活或抑制基因表达系统。