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Titolo:
Competitive and allosteric interactions in ligand binding to P-glycoprotein as observed on an immobilized P-glycoprotein liquid chromatographic stationary phase
Autore:
Lu, LL; Leonessa, F; Clarke, R; Wainer, IW;
Indirizzi:
Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 Res Ctr, Washington, DC 20007 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 1, volume: 59, anno: 2001,
pagine: 62 - 68
SICI:
0026-895X(200101)59:1<62:CAAIIL>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE TRANSPORTER; ATPASE ACTIVITY; BREAST-CANCER; AFFINITY-CHROMATOGRAPHY; ENDOTHELIAL-CELLS; SITES; VERAPAMIL; VINBLASTINE; MEMBRANE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Wainer, IW Georgetown Univ, Sch Med, Dept Pharmacol, Rm C305,Med Dent Bldg,3900 Reservoir Rd NW, Washington, DC 20007 USA Georgetown Univ Rm C305,MedDent Bldg,3900 Reservoir Rd NW Washington DC USA 20007
Citazione:
L.L. Lu et al., "Competitive and allosteric interactions in ligand binding to P-glycoprotein as observed on an immobilized P-glycoprotein liquid chromatographic stationary phase", MOLEC PHARM, 59(1), 2001, pp. 62-68

Abstract

A liquid chromatographic stationary phase containing immobilized P-glycoprotein (Pgp) was synthesized using cell membranes obtained from Pgp-expressing cells. The resulting Pgp-stationary phase was used in frontal and zonal chromatographic studies to investigate the binding of vinblastine (VBL), doxorubicin (DOX), verapamil (VER), and cyclosporin A (CsA) to the immobilized Pgp. The compounds were added individually to the chromatographic system with or without ATP in the running buffer. Using this approach, dissociation constants were calculated for VBL (23.5 +/- 7.8 nM), DOX (15.0 +/- 3.2 muM), VER (54.2 +/- 4.7 muM), and CsA [97.9 +/- 19.4 nM (without ATP) and 62.5 +/- 4.6 nM (with ATP)]. The compounds were also added in pairs using standard competitive chromatography procedures. The results of the study demonstrate that competitive interactions occurred between VBL and DOX, cooperative allosteric interactions occurred between VBL and CsA and ATP and CsA, and anticooperative allosteric interactions occurred between ATP and VBL and VER. The chromatographic studies indicate that the immobilized Pgp was modified by ligand and cofactor binding and that the stationary phase can be used to study drug-drug binding interactions on the Pgp molecule.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:01:25