膜蛋白稳定技术及其在药物筛选中的应用进展

Advancements in stabilization technologies for membrane protein and its application in drug screening

膜蛋白承担了生物膜的主要功能,是新药研发最重要的靶点群,大约60%的药物以膜蛋白为靶点。由于膜蛋白在水溶液中有明显的聚集和变性倾向,在体外很难模拟维持膜蛋白正确构象的类膜环境,导致膜蛋白的结构和功能以及相关配体药物的研究远远滞后于水溶性蛋白。膜蛋白稳定技术对于建立高专属性、高灵敏度和高通量的膜蛋白配体药物筛选方法具有重要的意义。本文综述了目前用于稳定分离纯化膜蛋白的一些技术,包括洗涤剂、人造膜、聚合物、慢病毒颗粒等,以及这些技术在药物筛选中的具体应用。

Membrane proteins are the main undertakers of biofilm function, and also the most important target group for innovative drug discovery and research. About 60% of drugs targets are membrane proteins. Due to the obvious aggregation and denaturation tendency of membrane proteins in aqueous solution, it is difficult to simulate the membrane like environment to maintain the correct conformation of membrane proteins in vitro, which results in the slower-growing research on the structure and function of membrane proteins and related ligand drugs than that of water-soluble proteins. Membrane protein stabilization technology is the premise of establishing high specificity, high sensitivity and high throughput drug screening methods for membrane protein ligands, which is of great significance. In this paper, some techniques for stable separation and purification of membrane proteins are reviewed, including detergents, artificial membranes, polymers, lentiviral particles and so on, as well as their specific applications in drug screening.