Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, Maharashtra, India.
School of Chemical and Materials Sciences, Indian Institute of Technology Goa, Ponda 403 401, Goa, India.
J Med Chem. 2020 Dec 24;63(24):15308-15332. doi: 10.1021/acs.jmedchem.0c01337. Epub 2020 Dec 13.
Tuberculosis (TB) remains one of the deadliest infectious diseases and begs the scientific community to up the ante for research and exploration of completely novel therapeutic avenues. Chemical biology-inspired design of tunable chemical tools has aided in clinical diagnosis, facilitated discovery of therapeutics, and begun to enable investigation of virulence mechanisms at the host-pathogen interface of . This Perspective highlights chemical tools specific to mycobacterial proteins and the cell lipid envelope that have furnished rapid and selective diagnostic strategies and provided unprecedented insights into the function of the mycobacterial proteome and lipidome. We discuss chemical tools that have enabled elucidating otherwise intractable biological processes by leveraging the unique lipid and metabolite repertoire of mycobacterial species. Some of these probes represent exciting starting points with the potential to illuminate poorly understood aspects of mycobacterial pathogenesis, particularly the host membrane-pathogen interactions.
结核病(TB)仍然是最致命的传染病之一,这促使科学界加大研究和探索全新治疗方法的力度。受化学生物学启发而设计的可调化学工具在临床诊断中提供了帮助,促进了治疗药物的发现,并开始使人们能够研究宿主-病原体界面的毒力机制。本观点重点介绍了针对分枝杆菌蛋白和细胞脂包膜的化学工具,这些工具提供了快速和选择性的诊断策略,并为研究分枝杆菌蛋白质组和脂质组的功能提供了前所未有的见解。我们讨论了通过利用分枝杆菌物种独特的脂质和代谢物组成来阐明原本难以处理的生物学过程的化学工具。其中一些探针代表了令人兴奋的起点,有可能阐明分枝杆菌发病机制中一些了解甚少的方面,特别是宿主膜-病原体相互作用。