物理化学学报 >> 2005, Vol. 21 >> Issue (02): 123-127.doi: 10.3866/PKU.WHXB20050203

研究论文 上一篇    下一篇

甲磺酸培氟沙星与人血清白蛋白之间结合模式的研究

马国正; 谭非; 蒋勇军; 郑柯文; 郭明; 俞庆森   

  1. 浙江大学理学院化学系,杭州 310027;浙江大学宁波理工学院药物分子设计与营养工程重点实验室,宁波 315100
  • 收稿日期:2004-06-08 修回日期:2004-08-17 发布日期:2005-02-15
  • 通讯作者: 蒋勇军 E-mail:yjjiang@nit.net.cn

The Binding Mode of Pefloxacin Mesylate with Human Serum Albumin

MA Guo-Zheng; TAN Fei; JIANG Yong-Jun; ZHENG Ke-Wen; GUO Ming; YU Qing-Sen   

  1. Department of Chemistry, Zhejiang University, Hangzhou 310027; Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100
  • Received:2004-06-08 Revised:2004-08-17 Published:2005-02-15
  • Contact: JIANG Yong-Jun E-mail:yjjiang@nit.net.cn

摘要: 采用实验和计算的方法研究了甲磺酸培氟沙星与人血清白蛋白之间的结合作用.荧光法测得甲磺酸培氟沙星与人血清白蛋白形成一种类型的复合物,结合常数为1.7×105 L•mol-1,有1.05个平均结合位点;微量热法测得该药物-蛋白结合过程中焓变为1.03 kJ•mol-1,熵变为101.28 J•K-1•mol-1,反应为熵驱动.用分子对接的方法预测了甲磺酸培氟沙星与人血清白蛋白的结合模式.计算表明,甲磺酸培氟沙星可结合在人血清白蛋白的两个药物结合位点,疏水作用即熵效应在药物与蛋白的结合中起重要作用,预测的结合自由能和实验值基本一致.

关键词: 甲磺酸培氟沙星, 人血清白蛋白, 分子模建, 结合模式

Abstract: This study was designed to explore the binding mode of pefloxacin mesylate(PFLX) with human serum albumin (HSA).Fluorescence spectroscopic results showed pefloxacin-HSA complex with binding constants of 1.7×105 L•mol-1.The enthalpy change (ΔrHm) and entropy change (ΔrSm) were measured by microcalorimetry to be 1.03 kJ•mol-1 and 101.28 J•K-1•mol-1,which indicated that hydrophobic interaction played a major role in the binding of PFLX with HSA. The possible binding domains of HSA for PFLX were studied by molecular modeling, which predicted that the hydrophobic interaction played a dominating role in this drug-protein interaction and PFLX could bind to Sudlow’s sites I and II of HSA. The binding energies obtained from the molecular modeling were in accordance with the experiment results.

Key words: Pefloxacin mesylate, Human serum albumin, Molecular modeling,  Binding mode