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

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Item Type:	Article
Title:	Identification and characterization of a single high-affinity fatty acid binding site in human serum albumin
Creators Name:	Wenskowsky, L., Schreuder, H., Derdau, V., Matter, H., Volkmar, J., Nazaré, M., 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
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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