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Contenuto archiviato il 2024-06-18

Carbohydrate Mimesis using Fluorinated Sugars for Chemical Biology: From Reaction Design to Applications in Molecular Imaging

Obiettivo

The principle objective of this proposal is to validate fluorinated glyco-structures as effective carbohydrate mimics for the next frontier in pharmaceutical research. Herein we propose to capitalise on the major advances in statistical data analysis which are unravelling the complexity of mammalian and bacterial “glycospace”. Molecular mimicry is a powerful drug design approach. It is therefore envisaged to develop a focussed programme of research to validate fluorinated glycostructures, and in particular 2-fluoro sugars, as carbohydrate mimics for chemical biology, exploiting the ubiquitous role of carbohydrates in molecular recognition. Salient features of the 2-fluoro substituent include (i) enhanced hydrolytic stability to enzymatic degradation, (ii) the presence of a NMR active reporter nucleus (19F) for facile analysis, and (iii) the possibility for molecular imaging application when using 18F labelled glycostructures. Phase one of this project will aim to develop synthetic routes to the target fluoro-glycostructures. This will involve a substantial component of physical organic chemistry including conformational analysis, advanced 19F NMR spectroscopy and the possible isolation of oxo-carbenium analogues by exploiting advances in the development of large, weakly co-ordinating anions. From first principle reaction design and development, through a basic understanding of conformation and reactivity, phase 2 will focus on the application of these materials for chemical biology applications. Phase 2 will then heavily focus on the application of complex oligosaccharides containing the PET active 18F moiety. It is envisaged that by exploiting the ubiquitous role of carbohydrates in molecular recognition that this would conceivably lead to the development of selective imaging agents, thus bypassing the current problem of relying on the metabolically controlled distribution of the commonly used PET tracer 2-fluorodeoxy glucose (18F-FDG).

Invito a presentare proposte

ERC-2013-StG
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Meccanismo di finanziamento

ERC-SG - ERC Starting Grant

Istituzione ospitante

UNIVERSITAET MUENSTER
Contributo UE
€ 1 253 880,00
Indirizzo
SCHLOSSPLATZ 2
48149 MUENSTER
Germania

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Regione
Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt
Tipo di attività
Higher or Secondary Education Establishments
Contatto amministrativo
Katharina Steinberg (Dr.)
Ricercatore principale
Ryan Gilmour (Prof.)
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)