Luminescence studies of binding affinity of vildagliptin with bovine serum albumin

Abstract

Vildagliptin (VDG)is a frontier drug for diabetes mellitus. It is prescribed both in the monotherapy as well as in an amalgamation with other antidiabetic drugs. Drug-serum protein binding is an essential parameter which influences ADME properties of the drug. In current study, binding of VDG with serum protein (bovine serum albumin: BSA) was investigated using multi-spectroscopic techniques. A computational approach was also employed to identify the binding affinity of VDG with BSA at both Sudlow I and II sites. An enzyme activity assay specific for esterase was also investigated to know the post-binding consequences of VDG with BSA. Fluorescence spectra of BSA samples treated with VDG shows static quenching with binding parameters for VDG-BSA complex show single class of equivalent binding stoichiometry(n = 1.331) and binding constant 1.1 x 104M−1 at 298.15 K. The binding constant indicates important role of non-polar interactions in the binding process. Fluorescence resonance energy transfer (FRET) analysis of VDG absorption spectra and emission spectrum of BSA confirmed no significant resonance in energy transfer. Synchronous fluorescence of BSA after binding with VDG show maximum changes in emission intensity at tryptophan (Trp) residues. Post binding with VDG, BSA conformation changes as suggested by circular dichorism (CD) spectra of BSA and this lead to enhanced protein stability as indicated by a thermal melting curve of BSA. Communicated by Ramaswamy H. Sarma