title: Spectroscopy and Molecular Modeling Study on the Interaction Between Mycophenolate Mofetil and Pepsin.
abstract: Mycophenolate mofetil (MMF) is an immunosuppressant used in clinical practice to limit the rejection of transplanted organs. MMF is absorbed and metabolized by the gastrointestinal tract and converted to mycophenolic acid by esterases in the plasma, liver, and kidney. Mycophenolic acid is the resulting active metabolite. The interaction of MMF with pepsin may affect the transfer and distribution of MMF. Given this effect, the present study investigated the interaction behavior between pepsin with MMF using docking simulation and spectroscopy method at different temperatures. The results of spectroscopy revealed that MMF has strong ability to quench the fluorescence of pepsin. The results also show that the acting force for binding was composed of hydrophobic forces. The three-dimensional fluorescence spectra and synchronous spectroscopy employed to determine the conformation showed that the binding of MMF with pepsin could induce MMF conformation and microenvironment changes. Furthermore, the molecular interaction distance and energy-transfer efficiency between pepsin and MMF were determined based on the Förster non-radiative energy-transfer mechanism. Docking simulation showed that MMF entered the hydrophobic cavity of pepsin, and a hydrogen bond was formed between the oxygen atoms of the carbanyl group of MMF and hydrogen atoms of tyrosine 189 of pepsin.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
authors.forename: Liuqi
authors.initials: L
authors.lastname: Guo
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: He
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China. lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D004735:Energy Transfer; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000737:chemistry* / Q000378:metabolism*; D010434:Pepsin A / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010434:Pepsin A; D009173:Mycophenolic Acid
keywords: Fluorescence spectroscopy; Interaction; Molecular modeling; Mycophenolate mofetil; Pepsin