Probing the binding dynamics of a sunitinib analog with human serum albumin: a combined spectroscopic and molecular docking approach
4 affiliations
- 1Analytical Chemistry Department, Egyptian Drug Authority (EDA) Giza Egypt.
- 2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University Kasr El-Aini St. Cairo 11562 Egypt [email protected].
- 3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Baha University Al-Baha 1988 Saudi Arabia.
- 4Pharmaceutical Chemistry Department, School of Pharmacy, New Giza University Giza Egypt.
Abstract
The study of protein binding, particularly interactions involving human serum albumin (HSA), is critical for elucidating drug performance and optimizing therapeutic efficacy. Given the profound impact of drug interactions with HSA on pharmacokinetic profiles, this study aims to characterize the binding interaction between a sunitinib analog (SA), as a promising chemotherapeutic drug candidate and HSA and to gain deeper understanding about the nature of binding interaction, binding constant, number of binding sites, binding location, and the conformational changes resulting from this interaction. The present study employs a comprehensive, multi-model approach. This methodology integrates fluorescence spectroscopy, UV absorption spectroscopy, Fourier-transform, and molecular docking, thereby providing a robust framework for detailed analysis. Fluorescence spectroscopy was implemented at three distinct temperatures to analyze the quenching mechanism and determine the binding constant (K b). SA can quench the native fluorescence of HSA through a static quenching mechanism. The K b value due to SA-HSA interaction was found to be of the order of 10⁴ M⁻¹ at 298 K, indicating the moderate affinity of SA to HSA. The negative values of ΔG° suggested that the interaction between SA and HSA was spontaneous. According to the thermodynamic analysis, SA binds HSA via van der Waals forces and H-bonding interactions. The findings of the ligand-competitive displacement experiment indicate that SA exhibits an affinity for HSA within the subdomain IIIA binding pocket. Analysis of data collected by multiple spectroscopic techniques revealed that SA induces perturbation in the secondary structure of HSA and modifies the polarity of the microenvironment surrounding tryptophan residues.
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BibTeX
@article{abbas2026probing,
title = {{Probing the binding dynamics of a sunitinib analog with human serum albumin: a combined spectroscopic and molecular docking approach}},
author = {Sohaila A Abbas and Eman A Mostafa and Alshaimaa M Alian and Ehab F Elkady and Marwa A Fouad},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra07888e},
url = {https://europepmc.org/article/PMC/PMC13725782},
note = {CC BY},
}
RIS
TY - JOUR
TI - Probing the binding dynamics of a sunitinib analog with human serum albumin: a combined spectroscopic and molecular docking approach
AU - Sohaila A Abbas
AU - Eman A Mostafa
AU - Alshaimaa M Alian
AU - Ehab F Elkady
AU - Marwa A Fouad
PY - 2026
DA - 2026/11/02
JO - RSC advances
DO - 10.1039/d6ra07888e
UR - https://europepmc.org/article/PMC/PMC13725782
AB - The study of protein binding, particularly interactions involving human serum albumin (HSA), is critical for elucidating drug performance and optimizing therapeutic efficacy. Given the profound impact of drug interactions with HSA on pharmacokinetic profiles, this study aims to characterize the binding interaction between a sunitinib analog (SA), as a promising chemotherapeutic drug candidate and HSA and to gain deeper understanding about the nature of binding interaction, binding constant, number of binding sites, binding location, and the conformational changes resulting from this interaction. The present study employs a comprehensive, multi-model approach. This methodology integrates fluorescence spectroscopy, UV absorption spectroscopy, Fourier-transform, and molecular docking, thereby providing a robust framework for detailed analysis. Fluorescence spectroscopy was implemented at three distinct temperatures to analyze the quenching mechanism and determine the binding constant (K b). SA can quench the native fluorescence of HSA through a static quenching mechanism. The K b value due to SA-HSA interaction was found to be of the order of 10⁴ M⁻¹ at 298 K, indicating the moderate affinity of SA to HSA. The negative values of ΔG° suggested that the interaction between SA and HSA was spontaneous. According to the thermodynamic analysis, SA binds HSA via van der Waals forces and H-bonding interactions. The findings of the ligand-competitive displacement experiment indicate that SA exhibits an affinity for HSA within the subdomain IIIA binding pocket. Analysis of data collected by multiple spectroscopic techniques revealed that SA induces perturbation in the secondary structure of HSA and modifies the polarity of the microenvironment surrounding tryptophan residues.
SN - 2046-2069
ER -