Abdelhameed Ali Saber, Nusrat Saima, Paliwal Sanjhi, Zaman Masihuz, Zaidi Nida, Khan Rizwan Hasan
a Department of Pharmaceutical Chemistry, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.
b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
Prep Biochem Biotechnol. 2017 Aug 9;47(7):655-663. doi: 10.1080/10826068.2016.1275014. Epub 2017 Jan 3.
Drug and protein interaction provides a structural guideline in the rational drug designing and in the synthesis of new and improved drugs with greater efficacy. We have examined here the interaction tendency and mechanism of nintedanib (NTB), an anticancer drug (tyrosine kinase inhibitor) with bovine serum albumin (BSA), by spectroscopic techniques. The decline in Stern-Volmer quenching constants and binding constant with the temperature rise suggests that BSA forms a complex with NTB. Binding constant obtained by modified Stern-Volmer equation at 3 temperatures was realized to be of the order of 10 M. Negative ΔG (-5.93 kcal mol), ΔH (-3.74 kcal mol), and ΔS (-1.50 kcal mol) values exhibited a spontaneous and exothermic reaction between BSA and NTB. NTB molecule interacts with BSA by forming hydrogen bonds, as elucidated by fluorescence results. Moreover, a minor increment in the helical conformation of BSA upon its binding to NTB was observed by circular dichroism spectroscopy. The modification in protein's symmetry and a decline in hydrodynamic radii were observed in the presence of NTB (from ~3.6 to ~3 nm) as obtained by the dynamic light scattering measurement results.
药物与蛋白质相互作用为合理药物设计以及合成疗效更佳的新型改良药物提供了结构指导。我们在此通过光谱技术研究了抗癌药物（酪氨酸激酶抑制剂）尼达尼布（NTB）与牛血清白蛋白（BSA）的相互作用趋势及机制。随着温度升高，斯特恩 - 沃尔默猝灭常数和结合常数下降，这表明BSA与NTB形成了复合物。通过修正的斯特恩 - 沃尔默方程在3个温度下获得的结合常数约为10⁶ M数量级。负的ΔG（约 - 5.93 kcal mol⁻¹）、ΔH（ - 3.74 kcal mol⁻¹）和ΔS（ - 1.50 kcal mol⁻¹ K⁻¹）值表明BSA与NTB之间发生了自发的放热反应。荧光结果表明，NTB分子通过形成氢键与BSA相互作用。此外，圆二色光谱观察到BSA与NTB结合后其螺旋构象略有增加。动态光散射测量结果显示，在NTB存在下，蛋白质的对称性发生改变，流体力学半径减小（从约3.6 nm降至约3 nm）。
