谱学与分子模拟研究甲磺酸酚妥拉明与肌红蛋白作用的分子机理  

Molecular Modeling and Spectroscopic Studies on the Interaction between Phentolamine Mesylate and Myoglobin

作　　者：毛慧[1] 孔凡彬[2] 赵国政[1] 赵波[1] 沈敬山[3] 

机构地区：[1]江苏省生物功能材料重点实验室南京师范大学化学与环境科学学院,南京210097 [2]河南科技学院资源与环境学院,新乡453003 [3]中国科学院上海药物研究所,上海201203

出　　处：《化学学报》2010年第15期1494-1498,共5页Acta Chimica Sinica

基　　金：国家自然科学基金(No20874047);江苏省重大研究计划(No08KJA430003);江苏省科技厅自然科学基金(NoK2009407)资助项目

摘　　要：利用紫外吸收光谱、荧光光谱结合分子模拟技术研究了在模拟生理条件下甲磺酸酚妥拉明(phentolamine mesylate,PM)与肌红蛋白(myoglobin,Mb)的作用机制.实验结果表明:药物小分子甲磺酸酚妥拉明与蛋白相互作用时结合位点数为1,表观结合常数KA为5.27×104L·mol-1.分子模拟结果表明:PM在Mb上的结合位点是site1活性口袋,两者通过疏水作用、亲水作用、氢键作用以及静电作用结合.PM与Mb中的氨基酸残基Trp,Tyr和Phe发生疏水相互作用,进而导致Mb的紫外吸收峰强度降低以及荧光的猝灭.它们之间负的ΔG值表明结合反应是热力学允许的。The molecular interaction mechanism of phentolamine mesylate（PM） with myoglobin（Mb） was investigated by UV absorption and fluorescence spectra in combination with molecular modeling under the simulated physiological conditions.The results revealed that the binding site number and apparent binding constant were 1 and 5.27×10^4 L·mol^-1,respectively.Furthermore,molecular modeling results indicated that PM could bind to the site 1 of Mb.Hydrophobic interaction,hydrophilic interaction,hydrogen bond formation and electrostatic interaction could account for the binding of PM.The hydrophobic interactions between the PM and Trp,Tyr,Phe of Mb lead to decrease of UV absorption and fluorescence quenching.Negative value of ΔG^- shows that the binding reaction is thermodynamically favorable.

关 键 词：甲磺酸酚妥拉明 肌红蛋白 相互作用 分子模拟 

分 类 号：R96[医药卫生—药理学]