Acta Pharmacologica et Toxicologica · 1971 · 10 citations · 5 references
Natural SciencesBiochemistryChemistryBiophysical ChemistryMolecular BiophysicsStructure-activity RelationshipsElectrostatic Interactions In BiomoleculesElectrostatics In BiomoleculesLigand BindingPartition CoefficientPka DeterminationProtein BindingConcentration-dependent BindingPh-dependent Binding KineticsPh-dependent Biomolecular InteractionsPhysicochemical PropertiesPhysiological Ph EffectsPka ValuesQuantum Mechanical ModelScatchard Analysis
Abstract: Thirteen sulfa drugs have been investigated. Their degree of binding to human serum albumin has been studied in vitro at varying pH. It was found that the degree of binding increased remarkably near the pKa value. A drug with a low pKa has a comparatively high degree of binding at physiological pH whereas a drug with a high pKa has a low degree of binding at this pH. It is shown that a good fit of experiments at a number of pH values is obtained when a modified Scatchard equation is used: image This shows that the uncharged species is hardly bound at all. The variation in binding ability among similar ions also depends on the hydrophobic bonds, which are correlated to the partition coefficient of the drug between octanol and water. A quantum mechanical approach has started which shows a correlation between degree of binding and distribution of electronic charge within the drug molecules. Some data are presented.
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