Investigation and comparison of the binding between tolvaptan and pepsin and trypsin: Multi‐spectroscopic approaches and molecular docking

Abstract

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.

Esterase activity and conformational changes of bovine serum albumin toward interaction with mephedrone: Spectroscopic and computational studies

“…As the concentration of 4MMC increases, the absorbance of BSA (5 μM) decreases from 280 to 269 nm, causing hypsochromic shift in the spectra, which showed conformational change in BSA upon binding with 4MMC. Also, the change in BSA absorbance suggests that the complex formation between BSA and 4MMC governs through static quenching mechanism …”

Development of highly selective and sensitive molecularly imprinted polymer-based electrochemical sensors for tolvaptan assay in tablets and serum

“…The analysis of TOL by spectroscopic, 4–6 chromatographic, 7–18 and electrochemical techniques 19 has been reported. The methods for determination of TOL have been discussed in terms of sample handling, cost, and sensitivity.…”

Evaluation of the Binding Properties of A New Phenylurea Appended Carbazole Compound to Pepsin/Trypsin by Computational and Multi-Spectral Analysis

“…Trypsin is a proteolytic enzyme that breaks down peptide bonds in the carboxylic groups of arginine, lysine and ornithine and has an optimum pH of 7.5-8.5. The trypsin active sites are formed by the three catalytic amino acid residues of Ser 195, Asp 102 and His 57 [23][24][25]. However, the interaction of ureacarbazole derivative with enzyme has not been extensively studied.…”