Unveiling the interaction mechanism of alogliptin benzoate with human serum albumin: Insights from spectroscopy, microcalorimetry, and molecular docking and molecular dynamics analyses

The interaction between a DPP-4 inhibitor, alogliptin benzoate (AB), and human serum albumin (HSA) was sys-tematically investigated via spectroscopy, microcalorimetry and molecular simulations. Steady-state fluorescence and time-resolved fluorescence spectrometry illustrated that the fluorescence quenching type of AB to HSA was static and caused by the formation of ground state AB-HSA complex. Isothermal titration calorimetry (ITC) combined with fluorescence spectra revealed that the affinity of AB to the subdomain IIA of HSA was moderate with a binding constant in the order of 104. Molecular docking analysis and thermodynamic parameters demonstrated that this combination was maintained by hydrogen bonding along with van der Waals force and hydrophobic force. Circular dichroism and three-dimensional (3D) fluorescence showed that AB increased the hydrophobicity of Trp residue and the alpha-helix content of HSA by 1.99%. Microdifferential scanning calorimetry revealed that the addition of AB enhanced the thermal stability of HSA. The action forces, binding stability, binding sites, and protein structure of the AB-HSA system were evaluated via molecular dynamics analysis in the simulated environment. On the basis of molecular docking, MD simulation constructed a more reliable 3D model of the AB-HSA complex in terms of spatial structure. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The interaction between a DPP-4 inhibitor, alogliptin benzoate (AB), and human serum albumin (HSA) was systematically investigated through spectroscopy, microcalorimetry, and molecular simulations. The study revealed that the interaction was maintained by hydrogen bonding, van der Waals force, and hydrophobic force, enhancing the hydrophobicity and thermal stability of HSA.