title: A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
abstract: The displacement of probes that bind selectively to subdomains IIA or IIIA on human serum albumin (HSA) by competing compounds has been followed using fluorescence spectroscopy, and has therefore been used to assign a primary binding site for these compounds in the presence and absence of fatty acids. The crystal structures have also been solved for three compounds: a matched pair of carboxylic acids whose binding strength to HSA unexpectedly decreased as the lipophilicity increased; and a highly bound sulphonamide that appeared not to displace the probes in the displacement assay. The crystallography results support the findings from the fluorescence displacement assay. The results indicate that drug binding to subdomain IB might also be important location for certain compounds.
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK104TG, England, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Buttar
authors.forename: Nicola
authors.initials: N
authors.lastname: Colclough
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerhardt
authors.forename: Philip A
authors.initials: PA
authors.lastname: MacFaul
authors.forename: Scott D
authors.initials: SD
authors.lastname: Phillips
authors.forename: Alleyn
authors.initials: A
authors.lastname: Plowright
authors.forename: Paul
authors.initials: P
authors.lastname: Whittamore
authors.forename: Kin
authors.initials: K
authors.lastname: Tam
authors.forename: Klaus
authors.initials: K
authors.lastname: Maskos
authors.forename: Stefan
authors.initials: S
authors.lastname: Steinbacher
authors.forename: Holger
authors.initials: H
authors.lastname: Steuber
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004347:Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D004364:Pharmaceutical Preparations; D012709:Serum Albumin