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Synthetic glycoproteins and their interactions with receptors studied by NMR

Objective

It is hard to overestimate the importance of glycoproteins as signalling molecules in Nature. Protein glycosylation is fundamental to many biologically essential processes and considering the increasing importance of glycosylation in therapeutic approaches, there is a need for novel methods for the preparation of glycoproteins in order to study their role in these cellular events, as well as to develop glycoproteins with therapeutic activities. Most glycoprotein production methods produce mixtures of glycoforms. However, combining chemical control of post-translational modifications (PTM) like glycosylation, with readily available protein scaffolds provides a systematic platform for creating probes (homogeneous glycoproteins) of protein–PTM interactions. To understand such interactions in biology, it is essential to study them from a structural and molecular point of view. In this project, the synthesis of naturally occurring carbohydrate-containing structures and their controlled conjugation with proteins will be carried out by means of the latest chemical and enzymatic approaches, rendering both oligosaccharides and synthetic glycoproteins amenable to be studied deeply in the context of protein-ligand binding. Well-established receptors like lectins will be selected at a first stage. A detailed picture of such interactions will be obtained through NMR experiments like STD or tr-NOESY. Additionally, the possibility to precisely incorporate synthetic carbohydrate structures containing labels, such as 13C, will greatly enhance such studies. Following these initial fundamental studies, medicinally relevant studies with e.g. selectins, siglecs, DC-SIGN and dectin will expand the project limit. The information obtained from the structural characterization of the protein-ligand binding will help to understand the role of glycoproteins in many cellular events and also in the development of new glycoproteins as therapeutics.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
Wellington Square University Offices
OX1 2JD Oxford
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 169 390,93
Administrative Contact
Linda Polik (Ms.)