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Content archived on 2024-04-16

Synthesis, structural analysis and biological properties of glycopeptides

Objective




Many proteins in nature are glycosylated on hydroxy-amino acids or asparagine sidechains. A large variety of different
oligosaccharides constitute the glycosyl part which is involved in many recognition and transport functions both inside the
cellular compartment and between the cells. However, in contrast to the globular protein counterpart which is often well
characterized, the precise structure and mechanism of interaction is not known for the oligosaccharides on the protein surface. Such characterization requires the access to a variety of large complex glycopeptides which can subjected to conformational
studies and used as model compounds in the biochemical
environment.
N- and O-Glycopeptides will be synthesized and applied as
inhibitors and substrates for enzymes, and the first target of this type will be the mucin type of O-glycopeptides and the
characterization of the glycosyltransferases involved in their biosynthesis. Attempts will be made to prepare aromatically
glycosylated peptides from the glycogen primer protein glycogenin in order to establish the minimal requirement for glycogen
polymerization.
The stimulation of cellular events by lectin binding will be investigated with artificial glycosylated peptide templates with a well characterized topography and flexibility. Ligands will constructed to physiological important mannose and galactose binding lectins, which require several clustered and arranged mannoses and galactoses for the binding.
The synthesis of modified analogues to naturally occurring
glycopeptides will be carried out and the synthetic analogues will be evaluated in affinity studies with their receptor
proteins. These may involve carbohydrate antibody interaction for which it is not clear what role the peptide backbone has in the binding.
All the synthesized glycopeptides will be analyzed by modern high field NMR-spectroscopy combined with computer simulations and the results will be correlated to the biological activity.
Apparatus for the effective automatic synthesis for a large
number of different glycopeptides will be developed.
Thus the application is concerned with the science of
gylcopeptides in a general sense, i.e. development of synthetic procedures, three dimensional structural analysis, and
physiological evaluation of biologically important glycopeptides. Emphasis will be on the synthesis and two research groups of different nationality (Denmark and Germany) will be
collaborating.

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CSC - Cost-sharing contracts

Coordinator

CARLSBERG LABORATORY
EU contribution
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Address
10,Gamle Carlsberg Vej 10
2500 VALBY
Denmark

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Total cost

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Participants (1)

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