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环丙沙星和致病菌铁结合蛋白的相互作用
唐文兵1,仲维清1*,赵靖霞2,杨根金2
0
(1.第二军医大学药学院无机化学教研室,上海 200433;2.第二军医大学药学院分析测试中心,上海 200433)
摘要:
目的:研究环丙沙星和致病菌铁结合蛋白之间的作用,探索致病菌铁结合蛋白(FBP)是否为环丙沙星的靶分子。方法:以紫外-可见分光光度法和核磁共振法,观察环丙沙星与从大肠杆菌表达出的淋病奈瑟双球菌的铁结合蛋白相互作用的结果。结果:在10 mmol/L、pH 7.40 Tris-HCl 缓冲溶液中,298 K时,环丙沙星与Fe3+形成配合物而将Fe3+从holo-FBP中脱去,当环丙沙星过量50倍时,可移去holo-FBP中一半量的Fe3+。结论:环丙沙星能部分脱去holo-FBP中的Fe3+,从而可干扰细菌对Fe3+的获取,进而可影响细菌的生长和致病能力。
关键词:  环丙沙星  铁结合蛋白  抗菌机制  紫外-可见分光光度法  磁共振波谱学
DOI:10.3724/SP.J.1008.2009.0808
投稿时间:2008-10-24修订日期:2009-02-20
基金项目:
Interaction between ciprofloxacin and ferric-ion binding protein from pathogenic bacteria
TANG Wen-bing1,ZHONG Wei-qing1*,ZHAO Jing-xia2,YANG Gen-jin2
(1.Department of Inorganic Chemistry,School of Pharmacy,Second Military Medical University,Shanghai 200433,China;2.Center of Analysis and Measurement,School of Pharmacy,Second Military Medical University,Shanghai 200433)
Abstract:
Objective:To investigate the interaction between ciprofloxacin (CIP) and ferric-ion binding protein (FBP) from pathogenic bacteria,so as to determine whether FBP is the target of CIP.Methods: Reactions between ciprofloxacin and FBP from N.gonorrhoeae,which was expressed in E.coli,were monitored by UV-visible and NMR spectroscopy.Results: Fe3+ was removed from holo-FBP by CIP in 10 mmol/L Tris-Cl buffer,pH 7.40,at 298 K,and half of the loaded Fe3+ was taken off when 50 molar equivalence of CIP was present.Conclusion: CIP can remove Fe3+ from holo-FBP,indicating that CIP can interfere with the Fe3+ capture of the bacteria and influence the growth and virulence of the bacteria.
Key words:  ciprofloxacin  ferric-iron binding protein  antibacterial mechanism  UV-visible spectroscopy  magnetic resonance spectroscopy