Chromatographic analysis of allosteric effects between ibuprofen and benzodiazepines on human serum albumin.
The effects of (R)- and (S)-ibuprofen on the binding of benzodiazepines to human serum albumin (HSA) were examined by biointeraction chromatography. The displacement of benzodiazepines from HSA by (R)- and (S)-ibuprofen was found to involve negative allosteric interactions (or possible direct competition) for most (R)-benzodiazepines. However, (S)-benzodiazepines gave positive or negative allosteric effects and direct competition when displaced by (R)- or (S)-ibuprofen. Association equilibrium constants and coupling constants measured for these effects indicated that they involved two classes of ibuprofen binding regions (i.e., low- and high-affinity sites). Based on these results, a model was proposed to explain the binding of benzodiazepines to HSA and their interactions with ibuprofen. This model gave good agreement with previous reports examining the binding of benzodiazepines to HSA.
Chen
Jianzhong
J
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Fitos
Ilona
I
Hage
David S
DS
D000494:Allosteric Regulation; D001569:Benzodiazepines / Q000737:chemistry*; D002846:Chromatography, Affinity; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D008140:Lorazepam / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D010076:Oxazepam / Q000031:analogs & derivatives / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D012709:Serum Albumin; C069005:lorazepam hemisuccinate; D001569:Benzodiazepines; C028246:oxazepam acetate; D010076:Oxazepam; D008140:Lorazepam; D007052:Ibuprofen