Characterization of the drug binding specificity of rat liver fatty acid binding protein

J Med Chem. 2008 Jul 10;51(13):3755-64. doi: 10.1021/jm701192w. Epub 2008 Jun 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilino Naphthalenesulfonates
  • Animals
  • Fatty Acid-Binding Proteins / chemistry*
  • Fatty Acid-Binding Proteins / metabolism*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Pharmaceutical Preparations / chemistry*
  • Pharmaceutical Preparations / metabolism
  • Protein Binding
  • Rats
  • Spectrometry, Fluorescence
  • Substrate Specificity


  • Anilino Naphthalenesulfonates
  • Fatty Acid-Binding Proteins
  • Ligands
  • Pharmaceutical Preparations
  • 1-anilino-8-naphthalenesulfonate