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GlycoPeptides

Exploiting in vitro evolution of macrocyclic glycopeptides to explore selectin interactions

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

GlycoPeptides project word cloud

Explore the words cloud of the GlycoPeptides project. It provides you a very rough idea of what is the project "GlycoPeptides" about.

technologies questions functioning macrocyclic sialyl glycosciences involve sorts core bio start tagged lectins lewisx tools proteins reprogramming orthogonal affinity pressure diverse carbohydrate kick ligands host selections medications combine synthetic types selectins scaffold random presented hopefully chemistry biological requirement power protein recruitment answers illuminate share shared tissues expertise moieties tyrosines many independent code library bear vitro cells background hugely evolution laboratory carbohydrates immune incorporated structures subsequent genetic binding gain glycoprotein abnormal alone epitope disease interaction career sufficient techniques peptide sulfotyrosines selectin bind sugar peptides tight sulfation implicated revealing technique genetically

Project "GlycoPeptides" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITEIT UTRECHT Organization address address: HEIDELBERGLAAN 8 city: UTRECHT postcode: 3584 CS website: www.uu.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]
Project website	https://sakjongkees.wixsite.com/website/investigating-selectin-interactions
Total cost	177˙598 €
EC max contribution	177˙598 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2016
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-05-01 to 2019-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITEIT UTRECHT UNIVERSITEIT UTRECHT Organization address address: HEIDELBERGLAAN 8 city: UTRECHT postcode: 3584 CS website: www.uu.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	NL (UTRECHT)	coordinator	177˙598.00

Map

Project objective

Many important biological processes involve binding of proteins to carbohydrates, including the recruitment of immune cells to tissues by proteins called selectins. The core binding requirement of all three types of selectins is a four sugar unit called the Sialyl LewisX epitope. However, affinity for this epitope alone is low. Further requirements for binding of selectins to their glycoprotein ligands include other carbohydrate and protein moieties, as well as sulfation of the carbohydrate or tyrosines. Open questions include what is necessary and sufficient for tight binding to each selectin, what sorts of ligands can bind to all selectins, and how the binding requirements can be presented on a synthetic scaffold. Answers to these questions will lead to a better understanding of the selectins, tools for future biological studies, and hopefully new medications for the many immune disease processes in which their abnormal functioning has been implicated.

I will combine my background in peptide selection technologies with the host expertise in lectins and bio-orthogonal chemistry to bring the power of evolution-based techniques to bear on these questions. Carbohydrates and sulfotyrosines will be incorporated in a scaffold of genetically tagged macrocyclic peptides, then selection pressure will be applied to a hugely diverse library of random structures. This will provide ligands that can bind to each selectin, as well as ligands that can bind to all selectins, and subsequent comparison of these ligands will illuminate the particular requirements for interaction with each selectin, as well as revealing shared features recognized by all. In addition to an increased understanding of the selectins, through this project I will gain new expertise in the glycosciences, share my unique experience with in vitro peptide selections using genetic code reprogramming – a technique not currently used in any laboratory in Europe – and kick-start my independent research career.

Publications

List of publications.
year	authors and title	journal	last update
2019	Lemeng Chao, Seino A. K. Jongkees High Throughput Approaches in Carbohydrate-Active Enzymology: Glycosidase and Glycosyl Transferase Inhibitors, Evolution, and Discovery published pages: , ISSN: 1433-7851, DOI: 10.1002/anie.201900055	Angewandte Chemie International Edition	2019-09-25

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The information about "GLYCOPEPTIDES" are provided by the European Opendata Portal: CORDIS opendata.