Characterization of the drug binding specificity of rat liver fatty acid binding protein.
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.
Chuang
Sara
S
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, Australia.
Velkov
Tony
T
Horne
James
J
Porter
Christopher J H
CJ
Scanlon
Martin J
MJ
D000817:Anilino Naphthalenesulfonates; D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
D000817:Anilino Naphthalenesulfonates; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D004364:Pharmaceutical Preparations; C027132:1-anilino-8-naphthalenesulfonate