Rehman, Fazal and Abubakar, Mujaheed and Ridzwan, Nor Farrah Wahidah and Mohamad, Saharuddin B. and Abd. Halim, Adyani Azizah and Tayyab, Saad (2024) Deciphering the binding mode and structural perturbations in floxuridine-human serum albumin complexation with spectroscopic, microscopic, and computational techniques. Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy, 308. ISSN 1873-3557, DOI https://doi.org/10.1016/j.saa.2023.123641.
Full text not available from this repository.Abstract
The binding mode of antineoplastic antimetabolite, floxuridine (FUDR), with human serum albumin (HSA), the leading carrier in blood circulation, was ascertained using multi-spectroscopic, microscopic, and computational techniques. A static fluorescence quenching was established due to decreased Ksv values with rising temperatures, suggesting FUDR-HSA complexation. UV-vis absorption spectral results also supported this conclusion. The binding constant, Ka values, were found within 9.7-7.9 x 103 M-1 at 290, 300, and 310 K, demonstrating a moderate binding affinity for the FUDR-HSA system. Thermodynamic data (Delta S = +46.35 J.mol-1.K-1 and Delta H =-8.77 kJ.mol-1) predicted the nature of stabilizing forces (hydrogen-bonds, hydrophobic, and van der Waals interactions) for the FUDR-HSA complex. Circular dichroism spectra displayed a minor disruption in the pro-tein's 2 degrees and 3 degrees structures. At the same time, atomic force microscopy images proved variations in the FUDR-HSA surface morphology, confirming its complex formation. The protein's microenvironment around Trp/Tyr resi-dues was also modified, as judged by 3-D fluorescence spectra. FUDR-bound HSA showed better resistance against thermal stress. As disclosed from ligand displacement studies, the FUDR binding site was placed in subdomain IIA (Site I). Further, the molecular docking analysis corroborated the competing displacement studies. Molecular dynamics evaluations revealed that the complex achieved equilibrium during simulations, confirming the FUDR-HSA complex's stability.
| Item Type: | Article |
|---|---|
| Funders: | Higher Education Commission of Pakistan |
| Uncontrolled Keywords: | Floxuridine; Human serum albumin; Fluorescence spectroscopy; Atomic force microscopy; Molecular dynamic simulations |
| Subjects: | Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Dentistry > Department of Oral & Craniofacial Sciences Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 27 Jun 2024 07:13 |
| Last Modified: | 03 Jul 2024 06:42 |
| URI: | http://eprints.um.edu.my/id/eprint/44259 |
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