6533b832fe1ef96bd129ad41

RESEARCH PRODUCT

Microseparation techniques for the study of the enantioselectivity of drug-plasma protein binding.

María José Medina-hernándezSalvador SagradoMaría Amparo Martínez-gómezRosa María Villanueva-camañasLaura Escuder-gilabert

subject

Drugmedia_common.quotation_subjectClinical BiochemistryAllosteric regulationPlasma protein bindingBiochemistryChromatography AffinityAnalytical ChemistryPharmacokineticsSpecies SpecificityDrug DiscoveryHumansAnimal speciesMolecular Biologymedia_commonPharmacologyChromatographyChemistryEnantioselective synthesisElectrophoresis CapillaryStereoisomerismGeneral MedicineBlood ProteinsBlood proteinsPharmaceutical PreparationsChromatography GelStereoselectivityAllosteric SiteProtein Binding

description

Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer–protein interactions, enantiomer–enantiomer interactions as well as chiral drug–drug interactions, including allosteric effects, is presented. The contribution of individual plasma proteins to the overall enantioselective binding and the animal species variability in drug–plasma protein binding stereoselectivity are reviewed. Copyright © 2008 John Wiley & Sons, Ltd.

10.1002/bmc.1134https://pubmed.ncbi.nlm.nih.gov/19016227