6533b872fe1ef96bd12d3834
RESEARCH PRODUCT
Influence of pH on the benzodiazepine-human serum albumin complex. Circular dichroism studies.
Werner E.g. MüllerUwe Wollertsubject
Circular dichroismNitrazepamChemical Phenomenamedicine.drug_classStereochemistryFlurazepamSize-exclusion chromatographyPlasma protein bindingFlurazepammedicineHumansBinding siteNitrazepamSerum AlbuminPharmacologyBenzodiazepineBenzodiazepinonesBinding SitesDiazepamChemistryOxazepamCircular DichroismOsmolar ConcentrationChlordiazepoxideGeneral MedicineBenzazepinesHydrogen-Ion ConcentrationHuman serum albuminChemistryKineticsBiophysicsmedicine.drugProtein Bindingdescription
The influence of pH on the binding of benzodiazepine derivatives to HSA was studied by circular dichroism measurements and by gel filtration. The binding of nearly all benzodiazepines is increased by rising the pH from 6.60 to 8.20. For flurazepam, clonazepam, and nitrazepam this increase in binding is due to an increase of the affinities, while for the other substances the affinity remains constant and the number of binding sites is increased from one to two. The changes in binding of the benzodiazepines by rising the pH are explained by a cationic amino acid residue near or at the benzodiazepine binding site of the HSA molecule. This second binding site is not detectable by circular dichroism. For several of the substances rising the pH from 6.60 to 8.20, is accompanied by large alterations of the optical properties of the HSA-benzodiazepine complexes. These alterations are explained by changes of the asymmetric environment of the benzodiazepine binding site at the HSA molecule in the structural transition at slightly alkaline pH values. To explain the different reactions of the benzodiazepines within the N→B transition a theory is given.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1974-05-27 | Naunyn-Schmiedeberg's archives of pharmacology |