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Spectroscopic and molecular docking studies for characterizing binding mechanism and conformational changes of human serum albumin upon interaction with Telmisartan.

光谱和分子对接研究表征人血清白蛋白与替米沙坦相互作用时的结合机制和构象变化。

  • 影响因子:3.48
  • DOI:10.1016/j.jsps.2020.04.015
  • 作者列表:"Bratty MA
  • 发表时间:2020-06-01
Abstract

:Human serum albumin (HSA), one of the most copious plasma proteins is responsible for binding and transportation of many exogenous and endogenous ligands including drugs. In this study, we intended to explore the extent and types of binding interaction present between HSA and the antihypertensive drug, telmisartan (TLM). The conformational changes in HSA due to this binding were also studied using different spectroscopic and molecular docking techniques. The spectral shifting and intensity variations upon interaction with TLM were studied using FT-IR spectroscopy. Binding constant and the change in absorption of HSA at its λmax was analyzed using absorption spectroscopy. Eventually, the types and extent of binding interactions were confirmed using molecular docking technique. Results have shown that TLM significantly interacts with the binding site-1 of HSA utilizing strong hydrogen bonding with Glu292, and Lys195 residues. The UV-absorption intensities were found to be decreased serially as the drug concentration increased with a binding constant of 1.01 × 103 M-1. The secondary structure analysis using FT-IR spectroscopy also revealed a marked reduction in the α-helix (56%) component of HSA on interaction. This study gives critical insights into the interaction of TLM with HSA protein which eventually affects the concentration of TLM reaching the site of action and ultimately its therapeutic profile.

摘要

: 人血清白蛋白 (HSA) 是最丰富的血浆蛋白之一,负责许多外源性和内源性配体 (包括药物) 的结合和转运。在本研究中,我们旨在探讨 HSA 与抗高血压药物替米沙坦 (TLM) 之间存在的结合相互作用的程度和类型。还使用不同的光谱和分子对接技术研究了由于这种结合引起的 HSA 构象变化。使用 FT-IR 光谱研究了与 TLM 相互作用时的光谱漂移和强度变化。结合常数和 HSA 在其 λ max 处的吸收变化使用吸收光谱分析。最终,使用分子对接技术确认了结合相互作用的类型和程度。结果表明,TLM 利用与 Glu292 和 Lys195 残基的强氢键与 HSA 的结合位点-1 显著相互作用。紫外吸收强度随着药物浓度的增加而逐渐降低,结合常数为 1.01 × 103 M-1。使用 FT-IR 光谱的二级结构分析也发现 HSA 的 α-螺旋 (56%) 组分在相互作用上显著减少。本研究对 TLM 与 HSA 蛋白的相互作用给出了重要的见解,HSA 蛋白最终影响 TLM 到达作用部位的浓度,并最终影响其治疗概况。

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