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SFB 670 TP AP1: Synthetic Nucleoside Analogs for the Activation of NOD Proteins
Project
Project code: DFG SFB 670
Contract period: 01.01.2006
- 31.12.2010
Purpose of research: Basic research
The modulation of specific biological function by means of small molecules opens important options for biomedical research and, in certain cases, even paves the way for the development of new therapeutic concepts. Within this project, synthetic organic chemistry will be used to generate libraries of small molecules, i.e. lipophilic carbocyclic nucleoside analogs. These compounds will then be used in the laboratories of partners within SFB 670 (M. Krönke, J. Parker) to study their ability to modulate the activity of NOD proteins, which are intracellular proteins involved in recognition of bacterial molecules and whose genetic variation has been linked to several inflammatory diseases.
As initial experiments have already shown, some carbocyclic nucleoside analogs have the ability to inhibit the TNF induced activation of NF-kB in a NOD1- or NOD2- dependent manner. By investigation (screening) of various synthetic nucleoside analogs (as NOD agonists or antagonists, respectively), the potential of this class of compounds will be further evaluated and structure-activity relationships will be identified - as a precondition for structural optimization. To be investigated in greater detail, most active compounds will be re-synthesized in larger amounts and labeled derivatives will be prepared.
Besides studying mammalian NOD proteins (T. Kufer and M. Krönke group), similar investigations will also be carried out using NOD proteins from plants (J. Parker group). This will allow the identification of common characteristics and differences in the activation of NOD Proteins in the differnt types of organisms.
Section overview
Subjects
- Biotechnology
