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Novel Chemical Probes for Tuberculosis Diagnosis and Treatment

Tuberculosis (TB) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis (MTB). In the developed world, the advent of powerful antibiotics and a concerted inoculation program saw the ne... ver más

26/03/2010

UOXF

178K€

Presupuesto del proyecto: 178K€

Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... 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 2010-03-26 No tenemos la información de la convocatoria

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UOXF

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Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 178K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Tuberculosis (TB) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis (MTB). In the developed world, the advent of powerful antibiotics and a concerted inoculation program saw the near extinction of TB. However, the rise of drug-resistant strains, HIV infections, and the neglect of TB control programs have increased the urgency for an alternative treatment and diagnosis. Since the presence of L-rhamnose and trehalose [α-D-Glc-(1↔1)-α-D-Glc] motifs in MTB have been associated with disease states, the preparation of modified derivatives constitute excellent research tools to investigate the infective process and offer themselves as potential therapeutic agents. These two sugars are not found in mammalian biology and therefore provide a powerful handle for distinguishing pathogen (MTB) from host (man) both during diagnosis and treatment. In particular, 2-deoxy-2-fluoroglycosides are compounds of increasing importance in biochemistry and medicinal research, especially as antiviral agents, cancer diagnosis probes, and labelling substrates for many biological studies. In addition, 2-deoxy-2-fluoroglycosides have been found particularly useful in the determination of the molecular mechanism of glycosidases and glycosyltransferases by trapping key enzymatic intermediates. We propose a program targeted at the development of innovative methodologies for the preparation of fluorosugars and glycolipid analogues that will allow direct imaging and treatment of TB. The specific goals include: a) Synthesis of 2-deoxy-2-fluoro-rhamnose and trehalose derivatives. b) Synthesis of CD1b-binding glycolipids with variations either at the glycoside and the lipid moieties. c) The use of fluoroglycosides as mechanistic probes, inhibitors, and imaging agents (alternative TB treatment and diagnosis: 18F PET and 19F NMR/MRI).

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