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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Chuang S,Velkov T,Horne J,Porter CJ,Scanlon MJdoi
10.1021/jm701192wsubject
Has Abstractpub_date
2008-07-10 00:00:00pages
3755-64issue
13eissn
0022-2623issn
1520-4804journal_volume
51pub_type
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