Insights into the interaction of methotrexate and human serum albumin: A spectroscopic and molecular modeling approach |
| |
Authors: | Li‐Yang Cheng Min Fang Ai‐Min Bai Yu Ouyang Yan‐Jun Hu |
| |
Affiliation: | 1. Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, People's Republic of China;2. Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Wuhan University, Wuhan, People's Republic of China |
| |
Abstract: | In this study, fluorescence spectroscopy and molecular modeling approaches were employed to investigate the binding of methotrexate to human serum albumin (HSA) under physiological conditions. From the mechanism, it was demonstrated that fluorescence quenching of HSA by methotrexate results from the formation of a methotrexate/HSA complex. Binding parameters calculated using the Stern–Volmer method and the Scatchard method showed that methotrexate binds to HSA with binding affinities in the order 104 L·mol?1. Thermodynamic parameter studies revealed that the binding reaction is spontaneous, and that hydrogen bonds and van der Waals interactions play a major role in the reaction. Site marker competitive displacement experiments and a molecular modeling approach demonstrated that methotrexate binds with appropriate affinity to site I (subdomain IIA) of HSA. Furthermore, we discuss some factors that influence methotrexate binding to HSA. |
| |
Keywords: | cyclodextrins HSA metal ions methotrexate molecular docking |
|
|