药物亲和反应的靶点稳定性技术及其应用研究进展

Drug affinity responsive target stability and its application:review

药物靶标是指存在于组织细胞内与药物相互作用,并赋予药物效应的特定分子,>98%药物靶标为蛋白质。药物与细胞内靶标相互作用,是药物发挥作用的基础。如何综合运用多种研究方法发现和确证药物作用新靶标是目前研究者面临的重要挑战。药物亲和反应的靶点稳定性(DARTS)技术是根据小分子药物与其靶标蛋白结合后导致对蛋白酶敏感性下降而发展起来的一项新技术,由于无需药物保护性修饰且无药物活性依赖性,因此可广泛应用于药物筛选与靶标鉴定。本文对DARTS技术的发现、技术原理及方法要点和应用进行综述。

A drug target refers to specific molecules that exist within tissue cells and interact with a drug to produce the drug effect. More than 98% of drug targets belong to protein. The interactions between a drug and the target in cells play a key role in the drug effect. How to use various methods to find and confirm the new target of a drug is one of the important challenges facing researchers. Drug affinity responsive target stability（DARTS）is a new technique based on the principle that when a small molecule compound binds to a protein,the interaction stabilizes the target protein′s structure so that it becomes protease resistant. This technique is universally applicable to drug screening and target identification because it requires no modification of the drug and is independent of the mechanism of drug action. This paper reviews the discovery of DARTS method,technical principles,methodology and its applications in researches.