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GlycoEdit SIGNED

New Chemical Tools for Precision Glycotherapy

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EC-Contrib. €

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Project "GlycoEdit" data sheet

The following table provides information about the project.

Coordinator
STICHTING KATHOLIEKE UNIVERSITEIT 

Organization address
address: GEERT GROOTEPLEIN NOORD 9
city: NIJMEGEN
postcode: 6525 EZ
website: www.radboudumc.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-11-01   to  2022-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    STICHTING KATHOLIEKE UNIVERSITEIT NL (NIJMEGEN) coordinator 1˙500˙000.00

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 Project objective

Glycosylation, the expression of carbohydrate structures on proteins and lipids, is found in all the domains of life. The collection of all glycans found on a cell is called the “glycome” which is information rich and a key player in a plethora of physiological and pathological processes. The information that the glycome holds can be written, read and erased by glycosyltransferases, lectins and glycosidases, respectively. The immense structural complexity and the fact that glycan biosynthesis is not under direct genetic control makes it very difficult to study the glycome. The glycosylation pattern of cancer cells is very different from that of healthy cells. It is still unclear whether aberrant glycosylation of cancer cells is a cause or consequence of tumorigenesis but it is associated with aggressive and invasive forms of cancer and hence poor prognosis. Malignant glycans are directly involved in a number of mechanisms that suppress the immune response, increase migration and extravasation (metastasis), block apoptosis and increase resistance to chemotherapy. The aim of this proposal is develop new glycomimetics that can be used to edit the glycome of cancer cells to target such evasive mechanisms. Using combinations of new glycan based inhibitors, a coordinated attack on the cancer glycome can be carried out which is expected to severely cripple the cancers ability to grow and metastasize. This will make the tumor more susceptible to immune mediated killing which may be further enhanced in combination with other anti-cancer strategies.

To minimize systemic side effects, new methods for the local delivery/activation of glycan inhibitors will be developed. The developed methods are expected to have a much broader than just cancer alone since the studied mechanisms are also associated with autoimmune and neurodegenerative disease.

 Publications

year authors and title journal last update
List of publications.
2019 Sam J. Moons, Rens A. Mensink, Jeroen P. J. Bruekers, Maurits L. A. Vercammen, Laura M. Jansen, Thomas J. Boltje
α-Selective Glycosylation with β-Glycosyl Sulfonium Ions Prepared via Intramolecular Alkylation
published pages: 4486-4500, ISSN: 0022-3263, DOI: 10.1021/acs.joc.9b00022
The Journal of Organic Chemistry 84/7 2020-02-18
2018 Hidde Elferink, Marion E. Severijnen, Jonathan Martens, Rens A. Mensink, Giel Berden, Jos Oomens, Floris P. J. T. Rutjes, Anouk M. Rijs, Thomas J. Boltje
Direct Experimental Characterization of Glycosyl Cations by Infrared Ion Spectroscopy
published pages: 6034-6038, ISSN: 0002-7863, DOI: 10.1021/jacs.8b01236
Journal of the American Chemical Society 140/19 2020-02-18
2019 Torben Heise, Johan F. A. Pijnenborg, Christian Büll, Niek van Hilten, Esther D. Kers-Rebel, Natasja Balneger, Hidde Elferink, Gosse J. Adema, Thomas J. Boltje
Potent Metabolic Sialylation Inhibitors Based on C-5-Modified Fluorinated Sialic Acids
published pages: 1014-1021, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b01757
Journal of Medicinal Chemistry 62/2 2020-02-18
2019 Hidde Elferink, Rens A. Mensink, Wilke W. A. Castelijns, Oscar Jansen, Jeroen P. J. Bruekers, Jonathan Martens, Jos Oomens, Anouk M. Rijs, Thomas J. Boltje
The Glycosylation Mechanisms of 6,3-Uronic Acid Lactones
published pages: 8746-8751, ISSN: 1433-7851, DOI: 10.1002/anie.201902507
Angewandte Chemie International Edition 58/26 2020-02-18
2019 Victor R. L. J. Bloemendal, Sam J. Moons, Jurriaan J. A. Heming, Mohamed Chayoua, Olaf Niesink, Jan C. M. van Hest, Thomas J. Boltje, Floris P. J. T. Rutjes
Chemoenzymatic Synthesis of Sialic Acid Derivatives Using Immobilized N‐ Acetylneuraminate Lyase in a Continuous Flow Reactor
published pages: , ISSN: 1615-4150, DOI: 10.1002/adsc.201900146
Advanced Synthesis & Catalysis 2020-02-18
2019 Sam J Moons, Gosse J Adema, Max TGM Derks, Thomas J Boltje, Christian Büll
Sialic acid glycoengineering using N-acetylmannosamine and sialic acid analogs
published pages: , ISSN: 1460-2423, DOI: 10.1093/glycob/cwz026
Glycobiology 2020-02-18

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