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DPRETB

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Cerrado

Exploring decaprenyl phosphoryl ribose epimerase DprE1 as a validated target f...

Exploring decaprenyl phosphoryl ribose epimerase DprE1 as a validated target for TB drug discovery Assay development high throughput screening and search for novel DprE1 inhibitor scaffolds Tuberculosis (TB) still claims 1.8 million deaths worldwide each year, and is the leading cause of infectious disease mortality by a bacterial pathogen. Current therapy for TB includes a combination of at least four different drug... ver más

30/04/2012

EPFL

174K€

Presupuesto del proyecto: 174K€

Líder del proyecto

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-04-30 No tenemos la información de la convocatoria

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

EPFL

0.00€ | Lider

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Líder del proyecto

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 174K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Tuberculosis (TB) still claims 1.8 million deaths worldwide each year, and is the leading cause of infectious disease mortality by a bacterial pathogen. Current therapy for TB includes a combination of at least four different drugs and has a duration of at least 6 months. There is an urgent need for novel drugs against TB, in order to fight this disease more efficiently and with shorter course treatments, therefore increasing the likelihood for their success. Here we propose to pursue a novel target for anti-TB drugs which was recently and fully validated, namely decaprenyl-phosphoryl ribose epimerase (DprE1), an enzyme that in conjunction with DprE2 catalyses the transformation of decaprenyl-phosphoryl ribose into decaprenyl-phosphoryl arabinose, in the arabinan biosynthetic pathway in Mycobacterium tuberculosis. Arabinan biosynthesis is essential for the assembly of the mycobacterial cell wall. A novel fluorescence polarization assay for DprE1 will be designed and optimized, involving the synthesis of fluorescent substrates, in order to overcome the complexity and low-throughput of the currently used TLC assay. The novel assay will be used for high-throughput screening of libraries of commercially available compounds in order to find novel DprE1 inhibitor scaffolds. Novel inhibitors that are amenable to structure-activity relationship studies will be subject to medicinal chemistry work in order to improve their potency against DprE1, and their anti-mycobacterial activity. This work will be performed at EPFL, in a close collaboration between the Global Health Institute and the Institute of Chemical Sciences and Engineering, in Prof. Stewart Cole and Prof. Paul Dyson’s laboratories, respectively.

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