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.
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