| Institution: | 1. School of Life Science, Liaoning University, Shenyang 110036, China;2. Experimental Center of Functional Subjects, China Medical University, 92 Bei Er Road, Heping District, Shenyang 110001, China;3. Centre for Biomedical Science Research, School of Clinical and Applied Sciences, Leeds Beckett University, City Campus, Leeds LS1 3HE, United Kingdom;1. Department of Physics, Bangalore Institute of Technology, Bangalore 560004, Karnataka, India;2. Department of Physics, M S Ramaiah Institute of Technology, Bangalore 560054, Karnataka, India;3. Department of Chemistry, R.V. College of Engineering, Bangalore 560059, Karnataka, India;1. Department of Chemistry, Central University of Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan 305817, India;2. Department of Chemistry, Washington University, One Brookings Drive, St. Louis, MO 63130-4899, United States;3. Department of Chemistry and Chemical Sciences, Central University of Jammu, Jammu 180011, India |
| Abstract: | A comparative biophysical study on the individual conformational adaptation embraced by two homologous serum albumins (SA) (bovine and human) towards a potential anticancer bioorganic compound 2-(6-chlorobenzod] thiazol-2-yl)-1H-benzode] isoquinoline-1,3(2H)- dione (CBIQD) is apparent from the discrimination in binding behavior and the ensuing consequences accomplished by combined in vitro optical spectroscopy, in silico molecular docking and molecular dynamics (MD) simulation. The Sudlow site I of HSA although anion receptive, harbors neutral CBIQD in Sudlow site I (subdomain IIA, close to Trp) of HSA, while in BSA its prefers to snugly fit into Sudlow site II (subdomain IIIA, close to Tyr). Based on discernable diminution of HSA mean fluorescence lifetime as a function of biluminophore concentration, facile occurrence of fluorescence resonance energy transfer (FRET) is substantiated as the probable quenching mechanism accompanied by structural deformations in the protein ensemble. CBIQD establishes itself within HSA close to Trp214, and consequently reduces the micropolarity of the cybotactic environment that is predominantly constituted by hydrophobic amino acid residues. The stronger association of CBIQD with HSA encourages an allosteric modulation leading to slight deformation in its secondary structure whereas for BSA the association is comparatively weaker. Sudlow site I of HSA is capable to embrace a favorable conformation like malleable gold to provide room for incoming CBIQD, whereas for BSA it behaves more like rigid cast-iron which does not admit any change thus forcing CBIQD to occupy an altogether different binding location i.e. the Sudlow site II. The anticancer CBIQD is found to be stable within the HSA scaffold as vindicated by root mean square deviation (RMSD) and root mean square fluctuation (RMSF) obtained by MD simulation. A competitively inhibited esterase-like activity of HSA upon CBIQD binding to Lys199 and Arg257 residues, plausibly envisions that similar naphthalimide based prodrugs, bearing ester functionality, can be particularly activated by Sudlow site I of HSA. The consolidated spectroscopic research described herein may encourage design of naphthalimide based pro-drugs for effective in vivo biodistribution using HSA-based drug delivery systems. |
