Investigation of Linagliptin-Human Serum Albumin Complex Formation using Spectroscopic Analysis and Molecular Docking

When human serum albumin binds firmly with a drug molecule, the impact will be greater on its half-life and other important pharmacokinetic properties. Linagliptin is an antidiabetic drug candidate with a good safety profile. The interaction mechanism of linagliptin with HSA is not reported so far. In the present study, various spectroscopic investigations (UV, fluorescence, FTIR and CD) and molecular docking were performed to determine the binding constant and the other binding characteristics of the interaction between HSA and drug molecule. The binding constant obtained from the UV-spectroscopic results (0.98x103 M-1), revealed weak binding between the protein and linagliptin structure. Fluorescence spectroscopy results showed quenching of intrinsic fluorescence of HSA through static quenching. The binding constant value was Ksv=1.26x10-4 M-1. In the FTIR and circular dichroism spectra minor changes were observed in peak positions and peak intensities. Molecular docking revealed that linagliptin was stabilized at site-I primarily with Pi-Pi stacking and the binding mode was similar that of R-warfarin.