Characterization of the Drug Binding Specificity of Rat Liver Fatty Acid Binding Protein

Abstract

Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an analogous function during the absorption of lipophilic drugs. Binding affinity for L-FABP was assessed by displacement of a fluorescent marker, 1-anilinonaphthalene-8-sulfonic acid (ANS), and the binding site location was determined via nuclear magnetic resonance chemical shift perturbation studies. It was found that the majority of drugs bound to L-FABP at two sites, with the internal site generally having a higher affinity for the compounds tested. Furthermore, in contrast to the interaction of L-FABP with fatty acids, it was demonstrated that a terminal carboxylate is not required for specific binding of lipophilic drugs at the internal site of L-FABP.

Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors

“…Prior reports have identified endogenous fatty acids and their derivatives, retinoic acid, and certain xenobiotics as ligands for FABPs (22,32,33). Our prior (6) and current study establish uncharged fatty acid amides as physiological ligands for FABPs.…”

Modulation of the Voltage-gated Potassium Channel (Kv4.3) and the Auxiliary Protein (KChIP3) Interactions by the Current Activator NS5806

“…For 1,8-ANS displacement studies, the excitation wavelength was set at 350 nm along the 2-mm path of a 0.2 ϫ 1-cm cuvette, and the integrated emission intensity (410 -500 nm) of 1,8-ANS bound to KChIP3 was used to calculate the extent of displacement. The dissociation constant of NS5806 for KChIP3 was recovered using a single binding site displacement equation (24),…”

Characterization of the Binding of Drugs to Human Intestinal Fatty Acid Binding Protein (IFABP): Potential Role of IFABP as an Alternative to Albumin for in Vitro-in Vivo Extrapolation of Drug Kinetic Parameters

“…The carboxylate head group of the fatty acid is deeply buried in the ligand binding site, where it hydrogen-bonds with Arg106 (Hamilton, 2004). Although it is known that rat IFABP and liver FABP (LFABP) bind a number of acidic and neutral drugs with varying affinities (Velkov et al, 2005(Velkov et al, , 2007Chuang et al, 2008), the binding of drugs to human IFABP has not been characterized.…”