靶分子亲和-质谱联用技术应用于中药等复杂体系中活性成分的筛选  

Target molecule affinity coupled with mass spectrometry for the screening of bioactive compounds in complex matrices

作　　者：李会军[1,2] 安婧婧[1] 周建良[1] 李萍[1,2] 

机构地区：[1]中国药科大学现代中药教育部重点实验室 [2]中国药科大学生药学与药用植物学教研室,南京210009

出　　处：《中国药科大学学报》2009年第2期97-103,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30772708;No.30873388)~~

摘　　要：如何从中药等复杂体系中快速、高效地筛选出活性成分,是现代药物研究的重要领域之一。基于光学检测或放射性检测的高通量药物筛选模式,在应用于中药等复杂体系时,由于没有成分分离过程,易产生假阳性或假阴性结果;而采用传统的成分分离、结构鉴定、活性测试的筛选模式,则存在工作量大、周期长、活性成分易丢失等缺陷。靶分子亲和-质谱联用技术是利用药物靶点与配体的亲和作用或靶酶的催化作用将活性成分从复杂体系中抽提出来,并用质谱对其进行检测及活性评价的一种筛选技术。本文对适用于中药等复杂体系中活性成分筛选的靶分子亲和-质谱联用技术进行了综述,主要介绍直接进样质谱筛选技术、膜分离-质谱联用技术、分子排阻色谱-质谱联用技术、固定化靶蛋白-质谱联用技术、前沿亲和色谱-质谱联用技术、高效液相色谱恒流在线反应-质谱联用技术等的原理及其应用,为中药活性成分筛选提供技术参考。Screening of the bioactive compounds from natural complex system, such as traditional Chinese medicines （TCM）, is one of the highlighted research challenges in the field of drug development. When encountered with complex matrices such as TCM extracts, high-throughput screening methods, mainly based on ultraviolet, flu- orimetric or radioactive detection, often led to false positive or negative results. At the same time, the traditional phytochemical screening procedure, i. e., isolation, structure elucidation and bioactivity test, had disadvantages including labor, time consumption, and bioactive compound degradation. Target molecule affinity coupled with mass spectrometry （MS） is becoming a new method for screening of bioactive compounds from complex matrices based on the affinity between the targets and ligands. This review covers the principle and the application of this screening technique, including direct infusion-MS, membrane separation-MS, size-exclusion chromatography-MS, immobilized target protein-MS, frontal affinity chromatography-MS and HPLC-continuous-flow enzyme assay-MS techniques.

关 键 词：药物靶点 靶分子亲和一质谱 中药 筛选 

分 类 号：R284.1[医药卫生—中药学]