Studies on the interactions between lactam analogs and the N-terminal extracellular tail of CC chemokine receptor 4 by CZE.
Electrophoresis
; 28(17): 3064-9, 2007 Aug.
Article
en En
| MEDLINE
| ID: mdl-17668450
CC chemokine receptor 4 (CCR4) is a kind of G-protein-coupled receptors with a characteristic seven-transmembrane structure and selectively expressed on Th2-type CD4+ T-cells, which play a pivotal role in allergic inflammation. In this study, the interactions between 2-(2-(2,4-dichloro-phenyl)-4-{[(2-methyl-3-chloro-phenyl)-1-ylmethyl]-carbamoyl}-methyl)-5-oxo-pyrrole-1-yl)-N-(3-piperidinyl-propyl)-acetamide (compound A), a known CCR4 antagonist, and ML40 were studied by CZE for the first time. Both qualitative and quantitative characterizations of the drug-peptide binding were determined. The binding constant of the interaction between the trans-diastereomer of compound A and ML40, calculated from the Scatchard plot by regression, was (1.06 +/- 0.11)x10(5)/M. Also, it was confirmed that the trans-diastereomer was more potent affinity with CCR4 than its cis-counterpart. The experimental results show that this reported method by CZE for the determination of the compound A and ML40 interactions is powerful, sensitive, and fast, requires less amounts of reagents, and further, it can be employed as one of the reliable screening methods to a series of lactam analogs in the drug discovery for allergic inflammation diseases.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Pirroles
/
Electroforesis Capilar
/
Receptores CCR4
Tipo de estudio:
Qualitative_research
Idioma:
En
Revista:
Electrophoresis
Año:
2007
Tipo del documento:
Article
Pais de publicación:
Alemania