Exploring the interaction between 'site-markers, aspirin and esterase-like activity' ternary systems on the human serum albumin: direct evidence for modulation of catalytic activity of the protein in different inhibition modes

摘要

Albumin which is the most abundant drug carrier protein in plasma controls the distribution aspect of drug pharmacokinetics. The aim of this study has been to elucidate the concurrent binding behavior of indomethacin/ibuprofen/heme to HSA under the effect of aspirin-mediated protein acetylation and also to explore the esterase-like catalytic property of the unmodified/modified proteins, as binary or ternary systems, by using various spectroscopic and molecular docking techniques. We found that aspirin-based modification of HSA affects the protein conformation as well as ligand binding at sites I-III. Decrease in pNPA-mediated esterase activity of HSA in different reversible inhibition modes, upon the protein-ligand interactions, was also documented, an issue that may receive considerable attention for computational prodrug design in near future.