论文部分内容阅读
药物筛选是整个药物发现过程的起点。在高通量和超高通量筛选中,建立准确、快速、微型化和无标记的分析化学方法是其核心内容。敞开式(常温常压)质谱于2004年提出后,因其可实现无需样品预处理的快速质谱分析而得到迅速发展;相对于电喷雾电离质谱,其基质效应小,分析速度快,已在不同形态样品快速分析、生物成像分析等领域发挥出重要作用。本研究将敞开式质谱作为高通量筛选的快速、无标记检测方法,结合高压液相色谱法分离在线结构鉴定及电雾式检测,获得分离化合物的分子量及绝对质量,结合活性筛选结果获取分离化合物的活性量效关系及活性动力学行为,从而建立针对天然产物复杂体系的新型高通量酶抑制剂筛选系统。
Drug screening is the starting point for the entire drug discovery process. At the heart of high-throughput and ultra-high-throughput screening is the establishment of accurate, rapid, miniaturized and label-free analytical chemistry. Open (normal temperature and pressure) mass spectrometry was developed in 2004 for rapid mass spectrometric analysis without sample pretreatment. Compared to electrospray ionization mass spectrometry, its mass effect is small and its analysis speed is fast. Rapid analysis of morphological samples, biological imaging analysis and other fields play an important role. In this study, open mass spectrometry was used as a rapid and unlabeled detection method for high-throughput screening. Based on on-line structural identification and electrospray ionization detection by HPLC, the molecular weight and absolute mass of isolated compounds were obtained. Compound activity and activity kinetic behavior, so as to establish a new high-throughput enzyme inhibitor screening system for complex systems of natural products.