Affinity and Specificity of Levamlodipine-Human Serum Albumin Interactions: Insights into Its Carrier Function

Abstract

The affinity and specificity of drugs with human serum albumin (HSA) are crucial factors influencing the bioactivity of drugs. To gain insight into the carrier function of HSA, the binding of levamlodipine with HSA has been investigated as a model system by a combined experimental and theoretical/computational approach. The fluorescence properties of HSA and the binding parameters of levamlodipine indicate that the binding is characterized by one binding site with static quenching mechanism, which is related to the energy transfer. As indicated by the thermodynamic analysis, hydrophobic interaction is the predominant force in levamlodipine-HSA complex, which is in agreement with the computational results. And the hydrogen bonds can be confirmed by computational approach between levamlodipine and HSA. Compared to predicted binding energies and binding energy spectra at seven sites on HSA, levamlodipine binding HSA at site I has a high affinity regime and the highest specificity characterized by the largest intrinsic specificity ratio (ISR). The binding characteristics at site I guarantee that drugs can be carried and released from HSA to carry out their specific bioactivity. Our concept and quantification of specificity is general and can be applied to other drug-target binding as well as molecular recognition of peptide-protein, protein-protein, and protein-DNA interactions.

Interaction of chlorogenic acids and quinides from coffee with human serum albumin

“…We have also verified that similar corrections were not necessary in all the other measurements. (Liu, Zheng, Yang, Wang, & Wang, 2009). The use of DMSO for the ligands solutions does not contribute to the blue shift, as we have verified by adding only DMSO in the same experimental conditions of all the titrations.…”

Fatty acid binding to serum albumin: Molecular simulation approaches

“…The HSA-ligand binding free energy (binding affinity) correlates with percentage plasma protein binding [143]. To date, calculated binding free energies have been reported for Gd-AAZTA complex (AAZTA = 6-amino-6-methylperhydro-1,4-diazepine tetraacetic acid) zidovudine and its derivatives [63], FAs (see section 3.2.2) [145], levamlodipine [76], flavones [78], perfluorooctanoic acid and perfluorooctane sulfonate [146], warfarin [147]. Fujiwara and Amisaki [147] have calculated binding free energies under various FA/HSA molar ratios, as described in section 3.2.…”

Uncovering the molecular and physiological processes of anticancer leads binding human serum albumin: A physical insight into drug efficacy

“…Usually, the types of interaction forces between small molecules and macromolecules mainly include hydrogen bonds, van der Waals forces, electrostatic interactions and hydrophobic interactions [18]. To estimate the binding mode, the thermodynamic parameters, Δ H , Δ S and Δ G are often considered.…”