title: Induced Europium Circularly Polarized Luminescence Monitors Reversible Drug Binding to Native α1-Acid Glycoprotein.
abstract: Alpha-1-acid glycoprotein (α1-AGP) is an important blood plasma glycoprotein. Following an acute-phase reaction such as stress, inflammation, burn, or infection, the bloodstream concentration of α1-AGP can increase up to 400 % of its normal concentration. A wide range of drugs is known to bind α1-AGP. Increased binding of pharmacologically active compounds to α1-AGP moderates their clinical effect by decreasing the amount of unbound drug in the bloodstream. This has important clinical ramifications for such applications as the duration of anesthesia and in determining dosage for drug therapy. In this study, the competitive binding to α1-AGP of a dynamically racemic europium(III) complex with seven pharmacologically active drugs absorbing in the range λ 250-290 nm was monitored by following changes in europium total emission and in induced circularly polarized luminescence (CPL). Binding affinities corresponding to Kdvalues in the range 0.5-100 μm were measured, in good agreement with published data.
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Jennings
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Waters
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Pal
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: David
authors.identifier: 0000-0001-5281-5146
authors.initials: D
authors.lastname: Parker
mesh_terms: D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005063:Europium / Q000737:chemistry*; D007700:Kinetics; D009961:Orosomucoid / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet
chemical_list: D056831:Coordination Complexes; D009961:Orosomucoid; D005063:Europium
keywords: CPL; chirality; drug binding; europium; luminescence