光谱法研究替硝唑与牛血清白蛋白的相互作用

Study on the Interaction of Tinidazole with Bovine Serum Albumin by Spectroscopic Methods

通过各种光谱方法研究替硝唑(TNZ)与牛血清白蛋白(BSA)的相互作用.用Stern-Volmer,Lineweaver-Burk和双对数方程计算了速率常数(Kq),猝灭常数(Ksv),静态荧光猝灭缔合常数(KLB),结合常数(Kb)和结合位点数(n).结果表明:TNZ能结合BSA.由于生成TNZ-BSA复合物,TNZ对BSA的猝灭是静态猝灭机理.热力学参数表明是一个自发过程,其作用力类型主要为疏水作用力.有一个结合位点.BSA的亚螺旋域ⅢA是主要结合位置,离酪氨酸残基更近.有弱的负协同作用.TNZ对BSA构象几乎不产生影响,Mg2+,Co2+,Fe3+,Ni2+,Mn2+和Cr3+对TNZ与BSA结合产生促进作用,延长药效时间.该实验对揭示药物动力学问题及后续硝基咪唑类药物的研发提供了理论依据.

The interactions of Tinidazole （ TNZ） with bovine serum albumin （ BSA） were investigated by vari-ous spectroscopic methods in this work. The rate constant （ Kq ） , quenching constant （ Ksv ） , static fluorescence quenching association constant （KLB）,binding constant （Kb） and binding site number （n） were calculated using Stern-Volmer, Lineweaver-Burk and double logarithm equations. The results from this study show that TNZ is able to bind with BSA. The probable quenching mechanism of BSA by TNZ is mainly the static quenching due to the for-mation of a TNZ-BSA complex. Our results of thermodynamic parameters indicate that the electrostatic force plays the main role in the binding process, which appears to be spontaneous. The obtained data for binding sites of n ap-proximately equal to 1 indicates that there is a single class of binding site for the BSA with TNZ. The primary bind-ing site of TNZ is located at the sub-domain ⅢA of BSA close to the tyrosine residue. There exists some weakly negative cooperative effect. The conjugation reaction would hardly affect the conformation of BSA. Mg2＋, Co2＋, Fe3＋, Ni2＋, Mn2＋and Cr3＋ promote the interaction of TNZ with BSA and prolong the drug effect time. This study provides a theoretical basis for the revelation of its pharmacokinetics as well as starting point for the further develop-ment of new nitroimidazoles drugs.