光谱法与计算机辅助研究α-西柏三烯二醇与牛血清白蛋白的相互作用

Multispectroscopic and Computational Study of the Interaction betweenα-Cembrenediol and Bovine Serum Albumin

α-西柏三烯二醇具有抗菌、抗肿瘤和神经保护等广泛生物活性,研究其与牛血清白蛋白(BSA)相互作用,有助于了解α-西柏三烯二醇在体内的转运、分布以及消除等信息。本研究通过紫外吸收光谱、荧光光谱、圆二色谱、分子对接模拟、分子动力学模拟等方法,在分子水平上研究了BSA与α-西柏三烯二醇在体外生理条件下的相互作用。结果表明,BSA与α-西柏三烯二醇发生了明显相互作用,且在293、303和310 K三个温度条件下,荧光淬灭常数KSV值和结合常数Kb值随着温度升高逐渐降低,α-西柏三烯二醇与BSA通过静态猝灭机制发生相互作用,三个不同温度下两者结合位点数n≈1,在BSA上只存在一个α-西柏三烯二醇的特异性结合位点;BSA与α-西柏三烯二醇的结合是自发进行的(ΔG<0),氢键和范德华力为主要驱动力(ΔH<0和ΔS<0);在Sudlow位点I处α-西柏三烯二醇与BSA发生结合;BSA与α-西柏三烯二醇结合导致其构象也会发生改变。本研究结果提供了α-西柏三烯二醇与BSA相互作用的基本信息,这将有助于进一步了解α-西柏三烯二醇的药代动力学特性。

α-Cembrenediol displays a diverse array of biological activities,encompassing antibacterial,antitumor,and neuroprotective effects.To comprehensively understand the in vivo transport,distribution,and elimination mechanisms associated withα-cembrenediol,its interaction with bovine serum albumin(BSA)was investigated.In this study,the interaction betweenα-cembrenediol and BSA was explored using various techniques,including UV absorption,steady-state fluorescence,circular dichroism spectrum,molecular docking,and molecular dynamics simulation.The results showed that there was a clear interaction between BSA andα-cembrenediol.Specifically,the KSV and Kb decreased with increasing temperature at 293,303,and 310 K,indicating thatα-cembrenediol interacted with BSA through a static quenching mechanism.Furthermore,the number of binding sites was approximately 1 at the three temperatures,suggesting the presence of a single specific binding site forα-cembrenediol on BSA.Moreover,the binding process occurred spontaneously(ΔG<0),primarily driven by hydrogen bonds and van der Waals forces(ΔH<0 andΔS<0).α-Cembrenediol bound to the Sudlow site I of BSA.Binding of BSA toα-cembrenediol also caused its conformation to change.This study provides essential insights into the interaction betweenα-cembrenediol and BSA,contributing to a better understanding of the pharmacokinetic properties of the compound.