Spectroscopic and molecular docking studies for characterizing binding mechanism and conformational changes of human serum albumin upon interaction with Telmisartan

Mohammed Al Bratty

doi:10.1016/j.jsps.2020.04.015

Spectroscopic and molecular docking studies for characterizing binding mechanism and conformational changes of human serum albumin upon interaction with Telmisartan

Saudi Pharm J. 2020 Jun;28(6):729-736. doi: 10.1016/j.jsps.2020.04.015. Epub 2020 May 6.

Author

Mohammed Al Bratty¹

Affiliation

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P. Box No. 114, Jazan, Saudi Arabia.

Abstract

Human serum albumin (HSA), one of the most copious plasma proteins is responsible for binding and transportation of many exogenous and endogenous ligands including drugs. In this study, we intended to explore the extent and types of binding interaction present between HSA and the antihypertensive drug, telmisartan (TLM). The conformational changes in HSA due to this binding were also studied using different spectroscopic and molecular docking techniques. The spectral shifting and intensity variations upon interaction with TLM were studied using FT-IR spectroscopy. Binding constant and the change in absorption of HSA at its λ_max was analyzed using absorption spectroscopy. Eventually, the types and extent of binding interactions were confirmed using molecular docking technique. Results have shown that TLM significantly interacts with the binding site-1 of HSA utilizing strong hydrogen bonding with Glu292, and Lys195 residues. The UV-absorption intensities were found to be decreased serially as the drug concentration increased with a binding constant of 1.01 × 10³ M^-1. The secondary structure analysis using FT-IR spectroscopy also revealed a marked reduction in the α-helix (56%) component of HSA on interaction. This study gives critical insights into the interaction of TLM with HSA protein which eventually affects the concentration of TLM reaching the site of action and ultimately its therapeutic profile.

Keywords: ADME, Absorption, Distribution, Metabolism, Excretion; Binding; FT-IR; Glu, Glutamate; HAS, Human Serum Albumin; Human serum albumin; Lys, Lysine; Molecular Docking; PDB, Protein Data Bank; TLM, Telmisartan; Telmisartan; UCSF, University of California, San Fransisco; UV–Vis; λmax, wavelength of maximum absorbance.