Spectroscopy and Molecular Modeling Study on the Interaction Between Mycophenolate Mofetil and Pepsin
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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.
KeywordsFluorescence spectroscopy Molecular modeling Mycophenolate mofetil Pepsin Interaction
This work was supported by the Applied Basic Research Project of Sichuan Province (Grant No. 2014JY0042), the Testing Platform Construction of Technology Achievement Transform of Sichuan Province (Grant No. 13CGPT0049), and the National Development and Reform Commission and Education of China (Grant No. 2014BW011).
- 3.Yang N, Wang J, Wang ZW, Wang QH, Yang HG, Wang XJ, Cheng MS (2012) Computational insights into the inhibition of inosine 5′-monophosphate dehydrogenase by mycophenolic acid analogs: three-dimensional quantitative structure–activity relationship and molecular docking studies. Chem Biol Drug Des 79:1063–1071CrossRefPubMedGoogle Scholar
- 14.Yang N, Wang J, Wang Z-W, Wang Q-H, Yang H-G, Wang X-J, Cheng M-S (2012) Computational insights into the inhibition of inosine 5'-monophosphate dehydrogenase by mycophenolic acid analogs: three-dimensional quantitative structure-activity relationship and molecular docking studies. Chem Biol Drug Des 79:1063–1071CrossRefPubMedGoogle Scholar
- 37.Förster T (1965) Delocalized excitation and excitation transfer. Academic Press, New YorkGoogle Scholar