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Functional Glycomics Through Chemoenzymatic Synthesis

Almost all cell surface proteins are modified by covalently-linked carbohydrates and the glycan structures on these glycoproteins are mediators of many physiological and disease processes. Despite their importance, there are no me... ver más

31/12/2026

3M€

Presupuesto del proyecto: 3M€

Líder del proyecto

UNIVERSITEIT UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-11-19

ERC-2020-ADG: ERC ADVANCED GRANT Specific Challenge:Objectives

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2 Participantes

2.50M€ | Lider

FREIXENET SA

429.93K€ | Participante

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Duración del proyecto: 61 meses Fecha Inicio: 2021-11-19
Fecha Fin: 2026-12-31

Líder del proyecto

UNIVERSITEIT UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Almost all cell surface proteins are modified by covalently-linked carbohydrates and the glycan structures on these glycoproteins are mediators of many physiological and disease processes. Despite their importance, there are no methods available to systematically and efficiently produce libraries of complex glycans to investigate specificities and biology of glycan binding proteins. To address this deficiency, we will develop chemoenzymatic technologies that can provide large collections of glycans having architectures of unprecedented complexity. It will exploit chemically modified sugar nucleotide donors that can be transferred by glycosyl transferases to give products in which artificial entities will blocks specific sites from enzymatic modification. It will provide full control over branching, sites of fucosylation, sulfation and sialylation. The chemical entities will be chosen in such a way that they can be removed after a series of enzymatic transformations. The methodology will be employed to prepare a series of keratan sulfate oligosaccharides. These glycoconjugates, which are biologically still poorly understood, have been implicated a multitude of physiological and disease processes. To further broaden the scope of the technology, a chemoenzymatic methodology will be developed to prepare sialosides that at C-4, C-7, C-8 and/or C-9 are modified by acetyl esters. The compounds will be used to develop a designer glycan microarray to identify ligands for glycan binding proteins. The focus will be on immuno-regulatory proteins and viruses that exploit cell surface glycans for infectivity. Cellular arrays will be developed to examine biological properties of hits identified in the microarray screening. The results of the studies will provide critical insight about glycan complexity and recognition by self- and viral glycan binding proteins, and will provide leads for the development of immune-modulators and antiviral agents.

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