Objective
In the post-genomic era, glycomics, the functional study of carbohydrates in living organisms, has received increasing attention for biological research and biomedical applications. The usual techniques in glycomics need the preparation and supply of pure sugar samples. For instance, carbohydrate microarrays, carrying tens or hundreds of different sugars that are bound covalently or noncovalently in small spots on solid surfaces, are becoming a standard tool for glycobiologists to screen carbohydrate-protein interactions in a high-throughput manner and determine structure-activity relationships for specific oligosaccharide sequences. However, the supply of hundreds/thousands of saccharides is required for wider applications of this novel technology. Here, it is proposed the development of novel and more efficient oligosaccharide synthetic approaches in order to speed the preparation of sugar probes and expand the utility of carbohydrate chips. We will focus on glycosaminoglycans (GAG) that are highly sulphated polysaccharides implicated in a plethora of biological processes, such as cellular growth and differentiation, pathogen infection, and tumor angiogenesis, by interaction with a wide range of proteins. Polymer-supported approaches, using polyethylene glycol (PEG)-grafted polystyrene (PS) resins, will be tested. Alternatively, tag-assisted solution-phase synthesis of oligosaccharides (using low-molecular-weight PEG chains or fluorous tags) will be also explored. The use of an acylsulfonamide linker compatible with the activation conditions of glycosyl trichloroacetimidates will be crucial to the success of the synthesis and the production of oligosaccharides containing a functionalized linker at the reducing end for conjugation purposes. The development of new protecting groups for sulphates will be also considered in order to introduce the sulphate groups at the monosaccharide stage and reduce the complexity of the final sulphation/deprotection steps.
Fields of science
Keywords
Call for proposal
FP7-PEOPLE-2007-2-2-ERG
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Funding Scheme
MC-ERG - European Re-integration Grants (ERG)Coordinator
28006 Madrid
Spain