Study on the molecular recognition action of lamivudine by human serum albumin

Abstract

In this work, the interaction of an anti-HIV drug lamivudine and human serum albumin (HSA) was studied by multispectroscopic and molecular modeling methods. The fluorescence emission spectra showed that the fluorescence of HSA was quenched by lamivudine through static mechanism with HSA-lamivudine complex produced at ground state. According to the binding equilibriums observed at 4 different temperatures, the number of binding site, binding constant, enthalpy change, entropy change, and Gibbs free energy change of the interaction were calculated. The results indicated that there was only 1 main binding site under present concentration condition, and then, the location of this binding site was ascertained by molecular probe experiments using warfarin and ibuprofen as site markers. The interaction was a spontaneous and exothermic process. Hydrogen bonds and van der Waals force were the major power that fixed lamivudine on Sudlow's site I in subdomain IIA of HSA molecule. The distance between donor and acceptor was determined by Förster's nonradiative fluorescence resonance energy transfer theory. Circular dichroism spectra exhibited the alteration of HSA's secondary structures. Molecular modeling investigation revealed the structure of HSA-lamivudine complex, including the conformation of lamivudine in binding site, the amino residues close to lamivudine, and the interaction forces between receptor and ligand. The study may be beneficial to therapists in understanding the distribution of lamivudine in vivo and explaining its drug-resistant mechanism in clinical diagnosis.

Spectroscopic and computational exploration of hypoxanthine riboside interacting with plasma albumin

“…In Figure , the significant red shift of λ max for the synchronous FLS of Δ λ at 60 nm (from 276 to 285 nm) and Δ λ at 15 nm (from 285 to 289 nm) suggested that these two residues had been transferred to more hydrophilic surroundings …”

“…Fluorescence spectra (FLS) were detected using a Hitachi F‐4600 spectrofluorometer. Emission spectra were obtained when excitation energy was set at 285 nm and the data used to calculate these results were corrected in accordance with a published equation to diminish any inner filter effect. CD measurements were carried out at 296 K on a Japanese Jasco J‐810 spectropolarimeter using 1.0‐cm quartz cells and under a nitrogen atmosphere.…”

“…HSA crystal structure was downloaded from the RCSB Protein Data Bank (PDB), with the ID 1H9Z. Docking parameters were based on our previous report with an exception for the location of the grid center, which was set at 35.444, 14.63 and 7.736 according to evidence from the probe experiments.…”

Integrated spectroscopic and computational analyses unravel the molecular interaction of pesticide azinphos‐methyl with bovine beta‐lactoglobulin

“…Fluorescence measurements have been widely utilized to evaluate the interaction of proteins with small molecules. 29 The BLG protein contains three chromophores that can exhibit fluorescence: tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe). These chromophores are sensitive to their environment.…”

“…Similar thermodynamic data were found when BLG interacted with rhein; the enthalpy and entropy values were positive, indicating that hydrophobic forces were the dominant forces in this interaction. 29…”