钙调素拮抗剂亲脂区与亲水区之间连接链距离的研究  

STUDIES ON THE MOST POTENT DISTANCE BETWEEN THE HYDROPHOBIC AND HYDROPHILIC GROUPS IN CALMODULIN ANTAGONIST

作　　者：雷小平[1] 张亮仁[1] 许凤荣[1] 

机构地区：[1]北京医科大学药学院,100083

出　　处：《北京医科大学学报》1997年第5期433-437,共5页Journal of Peking University(Health Sciences)

基　　金：国家自然科学基金!3930812

摘　　要：目的：研究钙调素拮抗剂亲脂区与亲水区之间连接链最佳的距离。方法：采用Fibonacci寻找法设计并合成了不同长度侧链的1，2－二苯乙烯类钙调素拮抗剂。结果：它们的拮抗活性表明，随着连接亲水部分氨基与亲脂苦环部分的碳链的增长，其活性增强。分子图形学研究显示，随着碳链的增长，氨基与钙调素Glu84，87的羧基的距离缩短，静电相互作用增强，拮抗剂与钙调素的结合能增加，并在碳链个数7左右达到一个极值。结论：在1，2-二苯乙烯类钙调素拮抗剂中，连接亲脂区与亲水区的脂肪链的碳原子的最佳个数在7左右。Objective: To find out the most potent distance between the hydrophobic and hydrophilic groups in calmodulin antagonist. Methods: Analogues of 1, 2-diphenyl ethylene with calmodulin antopnism were designed by Fibonacci searching method and syntheszed. Results: The antagonistic activities indicated that the antagonism improved with the increase of the chain length between the hydrophilic amine and hydrophobic aromatic groups. Computerized molecular modeling studies found that the electrostaitc interaction increased with the increase of the length of the carbon chain linkage, and got the maximun number of about 7 carbon.Conclusion: It was shown in this study that in this kind of calmodulin antagonist, the chain linkage length of about 7 carbons chain between hydrophilic and hydrophobic groups was expected to be most potent.

关 键 词：钙调蛋白 拮抗剂 亲脂区 分子图形学 中间连接链 

分 类 号：R972[医药卫生—药品] R914.4[医药卫生—药学]