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Titolo:
Comparison of the interaction of dopamine and high affinity positron emission tomography radiotracer fallypride with the dopamine D-2 receptor: a molecular modeling study
Autore:
Kapp, OH; Siemion, J; Kuo, J; Johnson, BA; Shankaran, V; Reba, RC; Mukherjee, J;
Indirizzi:
Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 nrico Fermi Inst, Chicago, IL 60637 USA Univ Chicago, Dept Radiol, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 ago, Dept Radiol, Chicago, IL 60637 USA Wright State Univ, Kettering Med Ctr, Dept Med Nucl Med, Dayton, OH 45429 USA Wright State Univ Dayton OH USA 45429 Med Nucl Med, Dayton, OH 45429 USA
Titolo Testata:
JOURNAL OF MOLECULAR MODELING
fascicolo: 1-3, volume: 7, anno: 2001,
pagine: 6 - 18
SICI:
1610-2940(2001)7:1-3<6:COTIOD>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS; LIGAND-BINDING; 3-DIMENSIONAL MODELS; AMINO-ACIDS; D2-DOPAMINE RECEPTORS; ANTAGONIST BINDING; SERINE RESIDUES;
Keywords:
dopamine D-2 receptor; fallypride; molecular modeling; ligand docking;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Kapp, OH Univ Chicago, Enrico Fermi Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA Univ Chicago 5640 S Ellis Ave Chicago IL USA 60637 , IL 60637 USA
Citazione:
O.H. Kapp et al., "Comparison of the interaction of dopamine and high affinity positron emission tomography radiotracer fallypride with the dopamine D-2 receptor: a molecular modeling study", J MOL MODEL, 7(1-3), 2001, pp. 6-18

Abstract

We have built a model of the D-2 dopaminergic receptor protein and have docked the agonist dopamine and two dopamine D-2 receptor antagonists, (S)-N-[(1-allyl-2-pyrrolidinyl)-methyl]-5-(3-fluoropropyl)- 2,3-dimethoxybenzamide (fallypride) and (S)-N-[(1-iso- butyl-2-pyrrolidinyl) methyl]-5-( 3-fluoropropyl)- 2,3-dimethoxybenzamide (ZYY-106), to its putative active site. Wehave utilized the structures of bacteriorhodopsin and rhodopsin for modeling the D-2 receptor by homology. Mutation studies and structure-activity studies have been used to refine our model further. Docking exercises of the ligands to the computer-generated D-2 model are used to explain the observed in vitro and in vivo behavior of these compounds. Interactions with the aspartate residue (Asp67) in helix-3 and the serine residues (serine-117 andserine-120) in helix-5 were observed for both dopamine and fallypride. A significant interaction of the phenyl ring of fallypride was observed with Phe121 and Trp155, which was weaker in the case of dopamine. The N-allyl group of fallypride is flanked by Phe158 and His162, possibly enhancing - interaction and the fluoropropyl group in fallypride is flanked by helix5: Pro124, helix5: phe125 and helix3: Ile75, which seem to form a pocket. These interactions may account for the higher affinity of fallypride for the D-2 receptor compared to dopamine.

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Documento generato il 02/10/20 alle ore 02:03:43