☆ 4.7 Article

Biomolecular interactions of amphotericin B nanomicelles with serum albumins: A combined biophysical and molecular docking approach

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY (2018)

Journal

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

Volume 205, Issue -, Pages 442-456

Publisher

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.saa.2018.07.057

Keywords

Amphotericin B; Bovine serum albumin; Human serum albumin; Drug-protein interaction; Experimental and computational approach; Spectroscopy

Funding

Prince of Songkla University
National Research Council of Thailand [PHA610372S]

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Abstract

In this work, we investigated the interaction of amphotericin B (AmB) nanomicelles on the binding affinity and conformational change of human serum albumin (HSA) in comparison with bovine serum albumin (BSA) under physiological conditions by conducting several spectroscopic techniques further confirmed through molecular docking approaches. The experimental results showed that AmB nanomicelles could bind to both HSA and BSA to form protein/drug complexes with one binding site, and the binding process was spontaneous under physiological conditions. Fluorescence studies revealed that the quenching mechanism of these complexes was static quenching rather than dynamic quenching and exhibited strong binding between serum albumin and AmB nanomicelles. The results from UV-Visible spectra, FT-IR spectra, and CD spectra revealed that the AmB formulations affected the structure of both HSA and BSA proteins by changing the microenvironment around the tryptophan residues of protein and caused a secondary structure change of the protein with the loss of helical stability. The molecular docking experiments also supported the above results and effectively proved the binding and changes in the conformation of serum albumins by AmB micelles. This finding provides information of in vitro drug-plasma protein interactions for further study on the AmB binding mechanism and the pharmacodynamics and pharmacokinetics. (C) 2018 Elsevier B.V. All rights reserved.

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Comprehending the intermolecular interaction of dacomitinib with bovine serum albumin: experimental and theoretical approaches

Zhe-Ying Hu, Wan-Jun Wang, Lu Hu, Jie-Hua Shi, Shao-Liang Jiang

Summary: Dacomitinib, a tyrosine kinase inhibitor, was found to quench the endogenous fluorescence of bovine serum albumin (BSA) through static quenching. It preferentially inserted into the hydrophobic cavity of the BSA subdomain IA (site III), forming a 1:1 DAC-BSA complex. DAC had a higher affinity for BSA, and non-radiative energy transfer occurred between them. Hydrogen bonds, van der Waals forces, and hydrophobic forces played a significant role in the insertion of DAC into the hydrophobic cavity of BSA. DAC affected the secondary structure of BSA, leading to a slight decrease in the alpha-helix content. The microenvironment around tyrosine residues was affected by the DAC-BSA combination, while the microenvironment around tryptophan residues remained unaffected. Molecular docking and molecular dynamics simulation confirmed the insertion of DAC into site III of BSA, with hydrogen energy and van der Waals energy contributing to the stability of the DAC-BSA complex. The influence of metal ions on the system's affinity was also explored.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2023)