光谱法研究酒石酸乙酰异戊酰泰乐菌素与牛血清白蛋白的相互作用及Zn^(2+),Cu^(2+)的影响（英文）

Characterization of the Interaction between Acetylisovaleryltylosin Tartrat and Bovine Serum Albumin without or with Zn^(2+) and Cu^(2+) by Spectroscopic Analysis

酒石酸乙酰异戊酰泰乐菌素(ATLL)是一种新的大环内酯类兽用抗菌药,研究ATLL与蛋白质的相互作用非常重要,这直接与ATLL在体内的药效相关。牛血清白蛋白(BSA)结构上与人血清白蛋白(HSA)同源,因此,常用它作研究药物与蛋白质相互作用的蛋白模型。血液中有许多金属离子,已有关于体内单一离子对药物与蛋白质相互作用影响的研究,采用多光谱方法对ATLL与BSA相互作用及Zn^(2+)和Cu^(2+)的影响进行研究。结果表明,BSA的荧光猝灭属于静态猝灭,Zn^(2+)和Cu^(2+)分别使有效猝灭常数降低和增大。主要的相互作用力为氢键和疏水作用力。ATLL改变蛋白质色氨酸和酪氨酸的微环境极性。紫外光谱分析发现,Cu^(2+)可能是通过Cu^(2+)-ATLL复合物以金属离子架桥作用来影响ATLL与BSA的作用,Zn^(2+)可能通过与ATLL的竞争作用结合BSA。红外光谱分析表明,ATLL使BSA的β-折叠和α-螺旋结构向β-转角和无规卷曲转变。这些基础数据有助于阐明在生理条件下,有无Zn^(2+),Cu^(2+)时ATLL与BSA的相互作用机制及金属离子在药物与蛋白质作用过程中对蛋白质功能的影响。

Acetylisovaleryltylosin tartrate （ATLL） is a new macrolide veterinary antibiotic ,it is necessary to study the binding of ATLL to protein ,which will directly correlate with the efficiency in vivo .Bovine serum albumin （BSA） is structure homologous with human serum albumin （HSA ） ,and is commonly chosen as a model to investigate drug-protein interaction .There are many metal ions in plasma ,as yet ,the studies on mainly focus on single metal ion .In this study ,the multiple systems formed by ATLL and BSA without or with Zn^2＋ and Cu2＋ have been studied by mult-spectroscopy .The results showed that ,the fluorescence of BSA was quenched by ATLL through a static quenching mechanism .The effective quenching constant （Ka ） of ATLL to BSA decreased with Zn^2＋ and increased with Cu^2＋ .Thermodynamic parameters revealed that hydro-gen bonds and hydrophobic forces played significant roles in the binding of ATLL to BSA .The polarity of tryptophan and tyrosine residues changed when adding ATLL with or without Zn^2＋ and Cu^2＋ .FT-IR spectra showed that ATLL changed α-helix andβ-sheet of BSA into β-turn and random structure .The UV-Vis spectra indicated that the effects of Zn^2＋ on ATLL binding to BSA may cause by a competition binding ,and Cu^2＋ pos-sibly formed Cu^2＋-ATLL complex via metal ion bridge .All the knowledge obtained in this work will be helpful to understand the transport mechanism of ATLL with BSA and the effect of metal ions on the interaction of drug-protein in vivo .