细胞器蛋白质的同位素标记定位：在药物发现研究中的现状和潜在应用。

Localization of Organelle Proteins by Isotope Tagging: Current status and potential applications in drug discovery research.

机构信息

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, United Kingdom; Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, United Kingdom.

出版信息

Drug Discov Today Technol. 2021 Dec;39:57-67. doi: 10.1016/j.ddtec.2021.06.003. Epub 2021 Jul 10.

DOI:10.1016/j.ddtec.2021.06.003

PMID:34906326

Abstract

Spatial proteomics has provided important insights into the relationship between protein function and subcellular location. Localization of Organelle Proteins by Isotope Tagging (LOPIT) and its variants are proteome-wide techniques, not matched in scale by microscopy-based or proximity tagging-based techniques, allowing holistic mapping of protein subcellular location and re-localization events downstream of cellular perturbations. LOPIT can be a powerful and versatile tool in drug discovery for unlocking important information on disease pathophysiology, drug mechanism of action, and off-target toxicity screenings. Here, we discuss technical concepts of LOPIT with its potential applications in drug discovery and development research.

摘要

空间蛋白质组学为研究蛋白质功能与亚细胞定位之间的关系提供了重要的见解。同位素标记定位细胞器蛋白质（LOPIT）及其变体是一种全蛋白质组范围的技术，在规模上无法与基于显微镜或邻近标记的技术相匹配，可全面绘制蛋白质亚细胞定位图谱，并对细胞扰动后的重定位事件进行定位。LOPIT 可以成为药物发现中的强大而通用的工具，可用于解锁有关疾病病理生理学、药物作用机制和脱靶毒性筛选的重要信息。在这里，我们将讨论 LOPIT 的技术概念及其在药物发现和开发研究中的潜在应用。