Spectroscopic and molecular docking approaches for investigating conformation and binding characteristics of clonazepam with bovine serum albumin (BSA)
Spectroscopic and molecular docking approaches for investigating conformation and binding characteristics of clonazepam with bovine serum albumin (BSA)
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DOI：
10.1016/j.jphotobiol.2016.12.029
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发表时间：
2017-02-01
影响因子：
5.4
通讯作者：
Shi, Jie-Hua
中科院分区：
文献类型：
--
作者：
Lou, Yan-Yue;Zhou, Kai-Li;Shi, Jie-Hua
氯硝西泮是一种苯二氮卓类药物，是一种经典的药物，用于预防和治疗癫痫发作、惊恐障碍、运动障碍等。为进一步阐明氯硝西泮在体内的分布及其药效学和药代动力学机制，采用紫外光谱、稳态荧光光谱、同步荧光光谱、三维荧光光谱、傅立叶变换红外光谱和分子对接等方法研究了氯硝西泮与牛血清白蛋白（BSA）的结合作用。结果表明，氯硝西泮通过货车力和氢键作用与BSA的Ⅲ A亚区（Site Ⅱ）结合，并通过静态猝灭过程猝灭BSA的内源荧光。在308 K时，氯硝西泮-BSA复合物的结合位点数（n）约为1，结合常数（K-b）约为7.94 × 104 M ~（-1）。氯硝西泮与牛血清白蛋白的结合过程是自发的，并且是自发驱动的过程，这是由于a，Δ G（0）< 0和16，|德尔塔H-0|> T| Delta S-0|，6531在所研究的温度范围内。同时，氯硝西泮与牛血清白蛋白的结合作用导致牛血清白蛋白的构象发生轻微变化，而氯硝西泮的构象发生明显变化，这表明氯硝西泮的柔性对提高氯硝西泮-牛血清白蛋白复合物的稳定性也起到了重要作用。(C)2016爱思唯尔B. V.保留所有权利。
Clonazepam, a type of benzodiazepine, is a classical drug used to prevent and treat seizures, panic disorder, movement disorder, among others. For further clarifying the distribution of clonazepam in vivo and the pharmacodynamic and pharmacokinetic mechanisms, the binding interaction between clonazepam and bovine serum albumin (BSA) was investigated using ultraviolet spectroscopy (UV), steady-state fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular docking methods. The results well confirmed that clonazepam bound on the subdomain III A (Site II) of BSA through van der Waals force and hydrogen bonding interaction, and quenched the intrinsic fluorescence of BSA through a static quenching process. The number of binding sites (n) and binding constant (K-b) of clonazepam-BSA complex were about 1 and 7.94 x 104 M-1 at 308 K, respectively. The binding process of clonazepam with BSA was spontaneous and enthalpy-driven process due to,a,Delta G(0) < 0 and 16,|Delta H-0| > T|Delta S-0|,6531 over the studied temperature range. Meanwhile, the binding interaction of clonazepam with BSA resulted in the slight change in the conformation of BSA and the obvious change in the conformation of clonazepam, implying that the flexibility of clonazepam also played an important role in increasing the stability of the clonazepam-BSA complex. (C) 2016 Elsevier B.V. All rights reserved.