Ziel
MicroRNAs have been identified as important endogenous regulators of gene function. Aberrant regulation of them has been linked to various human diseases. Small molecule intervention has the potential to provide a new therapeutic strategy. The aim of the project is the identification of selective microRNA modulators by fragment-based drug discovery (FBDD) approaches.
MicroRNAs are short ribonucleic acid (RNA) molecules, on average only 22 nucleotides long that act as post-transcriptional regulators by binding to complementary sequences in the three prime untranslated regions (3`UTRs) of target messenger RNA transcripts (mRNAs), usually resulting in efficient sequence-specific gene silencing, which is referred to as RNA interference (RNAi). The numerous reports indicating a role of microRNAs in connection with diseases such as diabetes, neurological disorders, and cancer raises the question whether microRNA could be targeted in the development of a novel therapeutic strategy.
Fragment-based drug discovery (FBDD) methods have been developed for finding lead compounds as part of the drug discovery process. The approach is based on identifying small molecules (with a molecular weight less than 250 Da and so called fragments), which generally bind only weakly to the biological target, and then iteratively elaborating them to produce successively more potent compounds.
The target microRNA will be microRNA-122, which plays a key role in hepatitis C virus infection, microRNA-155, an inducer of pancreatic cancer by suppressing the expression of cell-cycle protein p53 and let-7 microRNA, which has been shown to control the timing of development of nematode Caenorhabditis elegans from the last larval stage to adulthood.
Detailed binding studies will be done by NMR spectroscopy. In conclusion the druggability of microRNA will be proved.
Wissenschaftliches Gebiet
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicineneurology
- medical and health sciencesclinical medicineoncologypancreatic cancer
Thema/Themen
Aufforderung zur Vorschlagseinreichung
FP7-PEOPLE-2010-IEF
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
MC-IEF - Intra-European Fellowships (IEF)Koordinator
CB2 1TN Cambridge
Vereinigtes Königreich