Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Spectrochim Acta A Mol Biomol Spectrosc. 2017 Jun 15;181:254-263. doi: 10.1016/j.saa.2017.03.059. Epub 2017 Mar 28.
Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×10M), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
采用荧光、紫外-可见吸收、圆二色性（CD）和分子对接分析研究了多靶点抗癌药物舒尼替尼（SU）与人血清白蛋白（HSA）之间的结合研究。荧光猝灭数据和紫外-可见吸收结果表明形成了 SU-HSA 复合物。从 298K 时获得的结合常数（3.04×10M）值表明，SU 与 HSA 之间存在中等结合亲和力。从结合反应的热力学数据预测，SU-HSA 复合物形成过程中涉及疏水相互作用和氢键作为主要的分子间力。这些结果与分子对接分析吻合较好。SU 结合后，色氨酸和酪氨酸残基周围的微环境扰动以及 HSA 的二级和三级结构变化，从三维荧光和圆二色性结果中可以明显看出。SU 与 HSA 的结合也提高了蛋白质的热稳定性。竞争置换结果和分子对接分析揭示了 SU 与 HSA 在亚域 IIA（Sudlow 位点 I）的结合部位。还注意到一些常见离子对 SU-HSA 配合物结合常数的影响。
