Objective
Gleeman chains on the surface of mammalian cells are responsible for a variety of cell-cell recognition reactions. It is well established that a failure or disturbance of the biosynthesis of membrane associated carbohydrates leads to severe pathological conditions. More recently, it has been shown that the increased occurrence of distinct oligosaccharide motifs is responsible for the metastasis potential of particular tumour types. The increased biosynthesis of oligosaccharide epitomes is due an elevated expression of human glycosyltransferases. Therefore, the selective inhibition of human glycosyltransferases is an important and challenging topic that has the potential to pave the way for novel concepts in anti-tumour therapy. The ABO blood group galactosyltransferase and the human sialyltransferase hST3-Gal-lll where chosen as targets because of their biological significance. Both enzymes will be subjected to NMR studies with substrates and substrate analogues. With saturation transfer difference (STD) NMR techniques the binding epitomes of donor- and acceptor-substrates will be determined at atomic resolution. Transfer NOE experiments subsequently deliver information about the bioactive conformations of the substrates. Uniformly and specifically isotope enriched (15N, 13C, and 2H) ABO galactosyltransferase is produced in E.coli in very good yields. TROSY-type NMR experiments will allow to define the binding pocket of the enzyme. In conjunction with the knowledge about the binding epitomes of the legends this will yield additional valuable restraints for the design of potential glycosyltransferase inhibitors. The NMR results will be used to design small molecule inhibitors that will be synthesized, and in turn will also be subjected to NMR binding studies. The NMR studies will be complemented by additional techniques such as Biscoe experiments. It is envisioned that this iterative process leads to potent glycosyltransferase inhibitors.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences mathematics pure mathematics mathematical analysis
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
LUEBECK
Germany
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.