A fluorescence displacement assay for antidepressant drug discovery based on ligand-conjugated quantum dots.
J Am Chem Soc
; 133(44): 17528-31, 2011 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-21970724
ABSTRACT
The serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) protein plays a central role in terminating 5-HT neurotransmission and is the most important therapeutic target for the treatment of major depression and anxiety disorders. We report an innovative, versatile, and target-selective quantum dot (QD) labeling approach for SERT in single Xenopus oocytes that can be adopted as a drug-screening platform. Our labeling approach employs a custom-made, QD-tagged indoleamine derivative ligand, IDT318, that is structurally similar to 5-HT and accesses the primary binding site with enhanced human SERT selectivity. Incubating QD-labeled oocytes with paroxetine (Paxil), a high-affinity SERT-specific inhibitor, showed a concentration- and time-dependent decrease in QD fluorescence, demonstrating the utility of our approach for the identification of SERT modulators. Furthermore, with the development of ligands aimed at other pharmacologically relevant targets, our approach may potentially form the basis for a multitarget drug discovery platform.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paroxetina
/
Pontos Quânticos
/
Descoberta de Drogas
/
Fluorescência
/
Aminas
/
Antidepressivos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos