title: Quantitative analysis of allosteric drug-protein binding by biointeraction chromatography.
abstract: Allosteric interactions are important in many biological processes. They occur when the interactions of one substance with a binding agent changes the interactions of a second substance with the same agent at a separate site. Such interactions are often observed during the binding of drugs to blood proteins such as human serum albumin (HSA). Most previous studies of allosteric interactions have involved only qualitative observations of increased or decreased binding. In this study, we present an approach for quantitatively characterizing such allosteric effects using protein columns. The method is used to examine the interactions of ibuprofen/S-lorazepam acetate, S-oxazepam hemisuccinate/R-oxazepam hemisuccinate, and L-tryptophan/phenytoin during their binding to HSA. This approach can be applied to other receptors or biopolymers and can be used to independently examine the effects of two competing agents during an allosteric interaction.
authors.affiliation: Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Chen
authors.forename: David S
authors.initials: DS
authors.lastname: Hage
mesh_terms: D000495:Allosteric Site; D001665:Binding Sites; D001681:Biological Assay / Q000379:methods; D002846:Chromatography, Affinity / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D007052:Ibuprofen / Q000032:analysis / Q000737:chemistry; D010076:Oxazepam / Q000032:analysis / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D021281:Quantitative Structure-Activity Relationship; D012709:Serum Albumin / Q000032:analysis* / Q000737:chemistry; D013237:Stereoisomerism; D014364:Tryptophan / Q000032:analysis / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D010076:Oxazepam; D014364:Tryptophan; D007052:Ibuprofen