Chuang Sara, Velkov Tony, Horne James, Porter Christopher J H, Scanlon Martin J
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, Australia.
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.
肝脏脂肪酸结合蛋白（L-FABP）在肠细胞中含量很高，并且在脂肪吸收过程中参与脂肪酸的胞质溶解。在当前的研究中，已评估了L-FABP与一系列亲脂性药物的相互作用，以探索L-FABP在亲脂性药物吸收过程中发挥类似功能的可能性。通过荧光标记物1-苯胺基萘-8-磺酸（ANS）的置换来评估对L-FABP的结合亲和力，并通过核磁共振化学位移扰动研究确定结合位点的位置。结果发现，大多数药物在两个位点与L-FABP结合，内部位点通常对所测试的化合物具有更高的亲和力。此外，与L-FABP与脂肪酸的相互作用相反，已证明亲脂性药物在L-FABP内部位点的特异性结合不需要末端羧酸盐。
