title: Insights into the interaction of methotrexate and human serum albumin: A spectroscopic and molecular modeling approach.
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 104L·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.
authors.affiliation: Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, 435002, People's Republic of China.
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Cheng
authors.affiliation: Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, 435002, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, 435002, People's Republic of China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Bai
authors.affiliation: Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, 435002, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Department of Chemistry, Hubei Normal University, Huangshi, 435002, People's Republic of China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Hu
mesh_terms: D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D008670:Metals / Q000737:chemistry; D008727:Methotrexate / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D012709:Serum Albumin / Q000737:chemistry; D000075462:Serum Albumin, Human / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D047391:alpha-Cyclodextrins / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D008670:Metals; D012709:Serum Albumin; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; C040811:methotrexate-serum albumin; C031215:betadex; D008727:Methotrexate; C032613:alpha-cyclodextrin; D000075462:Serum Albumin, Human
keywords: HSA; cyclodextrins; metal ions; methotrexate; molecular docking