非肽类凝血酶抑制剂的比较分子力场分析  

Comparative Molecular Field Analysis of Non-peptidic Inhibitors of Thrombin

作　　者：韩晓峰[1] 刘莹[1] 高莹[1] 来鲁华[1] 

机构地区：[1]北京大学化学与分子工程学院分子动态与稳态结构国家重点实验室

出　　处：《化学学报》2003年第7期1136-1139,共4页Acta Chimica Sinica

基　　金：863高科技研究项目基金(No.2001AA235061)

摘　　要：在血栓症和止血疗法中凝血酶起重要的生物调节作用,凝血酶抑制剂由于其溶血栓作用成为药物设计的热点.对非肽类芳基磺酸酯系列凝血酶抑制剂进行了三维定量构效关系研究,用Autodock方法和比较分子力场分析相结合构建了该类分子的定量构效关系模型,得到三维等值线图.模型的传统相关系数r^2=0.956,交叉验证系数q^2=0.681,F_(4.16)=85.985,标准偏差S=0.158.该模型为凝血酶抑制剂的进一步结构改造提供了有益的启示.Thrombin is a trypsin-like serine proteinase that plays a crucial role in the processes of thrombosis and haemostasis. The three-dimensional quantitative structure activity relationship for a series of reported arylsulfonate based non-peptidic thrombin inhibitor. by comparative molecular field analysis have been studied. One representative compound of the series was docked onto thrombin (PDB code: 1UVT) by using Autodock program to determine the most likely binding conformation to thrombin. The strategy of all-orientation search (AOS) and all-placement search (APS) were used in the CoMFA study to give a final model with q(2) = 0.681, r(2) = 0.956 S = 0.158, and F-4,F-16 85.985. The analysis of the CoMFA coefficients map gives insights to the design of better thrombin inhibitors.

关 键 词：非肽类凝血酶抑制剂 比较分子力场分析 结构 血栓症 止血疗法 三维定量构效关系 

分 类 号：TQ464[化学工程—制药化工]