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Identification and characterization of a single high-affinity fatty acid binding site in human serum albumin

Item Type:Article
Title:Identification and characterization of a single high-affinity fatty acid binding site in human serum albumin
Creators Name:Wenskowsky, L. and Schreuder, H. and Derdau, V. and Matter, H. and Volkmar, J. and Nazaré, M. and Opatz, T. and Petry, S.
Abstract:A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C(12) fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein interaction, which are important prerequisites for modulation of drug pharmacokinetics.
Keywords:Binding Sites, Drug Interactions, Fatty Acids, Human Serum Albumin, NBD Labels
Source:Angewandte Chemie International Edition
ISSN:1433-7851
Publisher:Wiley-VCH (Germany)
Volume:57
Number:4
Page Range:1044-1048
Date:22 January 2018
Official Publication:https://doi.org/10.1002/anie.201710437
PubMed:View item in PubMed

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