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Investigation and comparison of the binding between tolvaptan and pepsin and trypsin: Multi‐spectroscopic approaches and molecular docking
Author(s) -
Ma Xiangling,
He Jiawei,
Huang Yanmei,
Xiao Ying,
Wang Qing,
Li Hui
Publication year - 2017
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2598
Subject(s) - chemistry , pepsin , trypsin , fluorescence spectroscopy , hydrogen bond , hydrophobic effect , quenching (fluorescence) , docking (animal) , van der waals force , chromatography , fluorescence , biochemistry , enzyme , organic chemistry , molecule , medicine , physics , nursing , quantum mechanics
Tolvaptan (TF), a selective arginine vasopressin V2 receptor antagonist, was approved by the Food and Drug Administration in 2009. This study mainly investigated the differences between the binding of TF with pepsin and trypsin by using a series of spectroscopy and molecular modeling methods. Thermodynamic parameters and molecular docking results suggested that the binding of TF to pepsin and trypsin were both spontaneous but driven by different forces. For pepsin, the binding was driven by hydrogen bonds and van der Waals forces; but for trypsin, it was driven by electrostatic forces and hydrophobic forces. The quenching mechanism between TF and pepsin and trypsin was investigated by fluorescence experiments and time‐resolved fluorescence spectroscopy. Synchronous fluorescence and 3‐dimensional fluorescence were used to investigate the micro‐environmental and conformational changes of pepsin and trypsin after the insertion of TF. In addition, activity‐measurement results showed that both the pepsin and trypsin activities increased with increasing TF concentration, which may help to understand the possible effect of TF on the digestion and absorption of nutrients in vivo.