LAUSR

The principal intent of this work is to explore whether the site-specific binding of a newly synthesized quinoline-appended anthracenyl chalcone, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ), with an extracellular protein of the human circulatory system, human serum albumin (HSA), can control the rotamerization of its sole tryptophan residue, Trp-214. With this aim, we have systematically studied the binding affinity, interactions, and localization pattern of the title compound inside the specific binding domain of the transport protein and any conformation alteration caused therein. Multiple spectroscopic experiments substantiated by an in silico molecular modeling exercise provide evidence for the binding of the guest ADMQ in the hydrophobic domain of HSA, which is primarily constituted by residues Trp-214, Arg-218, Arg-222, Asp-451, and Tyr-452. Rotationally restricted ADMQ prefers to reside in Sudlow site I (subdomain IIA) of HSA in close proximity (2.45 nm) to the intrinsic fluorophore Trp-214 and is interestingly found to control its vital rotamerization process. The driving force for this rotational interconversion is predominantly found to be governed by the direct interaction of ADMQ with Trp-214. However, the role of induced conformational perturbation in the biomacromolecule itself upon ADMQ adoption cannot be ruled out completely, as indicated by circular dichroism, 3D fluorescence, root-mean-square deviation, root-mean-square fluctuation, and secondary structure element observations. The comprehensive spectroscopic study outlined herein provides important information on the biophysical interaction of a chalcone-based potential therapeutic candidate with a carrier protein, exemplifying its utility in having a regulatory effect on the microconformations of Trp-214.