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Pyrophosphate Surrogates with Low polarity as part of glycosyltransferase ligands

Project description

Improved inhibitors against glycosyltransferase enzymes

Many diseases are characterised by a deregulation in the expression or activity of glycosyltransferase enzymes (GTs), which culminates in abnormal glycosylation. Interfering with these enzymes through the development of targeted GT inhibitors has opened new therapeutic avenues for these diseases. However, GT inhibitors must have the capacity to cross the cell membrane in order to have in vivo biological application. To address this, scientists of the EU-funded PyroSuL project are designing new synthetic building blocks that could be used as surrogates for the pyrophosphate moiety in GT inhibitors. Candidates demonstrating high substrate affinity and improved membrane permeability properties will be further exploited for the therapeutic targeting of GTs.

Objective

PyroSuL (Pyrophosphate Surrogates with Low polarity as part of glycosyltransferase ligands) is a project focused on the development of synthetic building blocks acting as surrogates for the pyrophosphate moiety in glycosyltransferase inhibitors. The final aim of this project is obtaining less polar ligands and inhibitors able to permeate across cellular membranes, which is the bottleneck for these inhibitors to have in vivo biological application. Through structure-based design, new surrogates will be explored. Interaction studies will be carried out through firstly computational approaches, and spectroscopic (nuclear magnetic resonance) and spectrometric (mass spectrometry) techniques will be employed. Surrogates showing promising affinity with the pyrophosphate recognition zone will be synthetically incorporated to substrate-like compounds, bearing a nucleoside and a carbohydrate or mimic. Final derivatives are supposed to show good protein affinities and membrane permeability properties.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITY OF EAST ANGLIA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 933,76
Address
EARLHAM ROAD
NR4 7TJ NORWICH
United Kingdom

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Region
East of England East Anglia Norwich and East Norfolk
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 933,76
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