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Identification and Characterization of a Single High‐Affinity Fatty Acid Binding Site in Human Serum Albumin
Author(s) -
Wenskowsky Lea,
Schreuder Herman,
Derdau Volker,
Matter Hans,
Volkmar Julia,
Nazaré Marc,
Opatz Till,
Petry Stefan
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201710437
Subject(s) - human serum albumin , chemistry , binding site , dissociation constant , fatty acid , albumin , plasma protein binding , serum albumin , ligand (biochemistry) , fatty acid binding protein , drug , titration , biochemistry , stereochemistry , receptor , biology , pharmacology , organic chemistry , gene
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.