单环β-内酰胺对大肠杆菌受体作用三维构效关系的比较分子力场分析(CoMFA)  

COMPARETIVE MOLECULE FORCE FIELD ANALYSIS (CoMFA) STUDY OF MONOCYCLIC β-LACTAM AGAINST E.Coli. RECEIPTER

作　　者：胡键[1] 李恒光[2] 吴彤[2] 谢如刚[1] 吕丁[2,3,4] 

机构地区：[1]四川大学化学学院,成都610064 [2]四川抗菌素工业研究所,成都610051 [3]3D-定量构效关系 [4]比较分子力场分析(CoMFA)

出　　处：《四川大学学报（自然科学版）》2001年第2期220-225,共6页Journal of Sichuan University(Natural Science Edition)

基　　金：国家新药研究开发基金!(959010581).

摘　　要：模拟受体活性部位与配体分子间作用的势场模型，从三维空间进一步探讨单环β－内酰胺抗生素构效关系，指导新化合物设计与合成．我们根据活性类似物原理，采用比较分子力场分析（ＣｏＭＦＡ）方法，对已知的２６个单环β－内酰胺化合物对大肠杆菌作用的构效关系进行了研究．模拟了大肠杆菌青霉素结合蛋白（ＰＢＰｓ）与配体分子间的作用力场和静电力场模型．该模型有利于指导新型β－内酰胺抗生素ｍｅ－ｔｏｏ类药物的设计．To simulate the potential field mold of interaction between th e active part of receptor and ligands, study in further the structure-activity relation in 3D, so as to direct new compounds design and synthesis. According to the principle of active analogues with similarity structure, Comparative Molecu lar Force Field Analysis (CoMFA) has been used to study the 3-dimension quantit ative structure activity relationship (3D-QSAR) of 26 monocyclic beta-lactam. Established and simulated the fields of steric and electrostatic mold of recepto r penicillin binding proteins (PBPs) interact with E.Coli. This mold is prof itable to direct the design of novel compounds.

关 键 词：Β-内酰胺抗生素 3D-定量构效关系 比较分子力场分析 CoMFA大肠杆菌 抗菌活性 药物代谢动力学 

分 类 号：R978.1[医药卫生—药品] R969.1[医药卫生—药学]