DFG FOR 1406 TP2: (Bio)Synthese von Tubulysin Derivaten für biologische und Biosynthese-Studien
Natural products play an important role in drug discovery and biomedical research for two major reasons: Firstly, they possess an enormous structural diversity serving as privileged scaffolds in drug discovery (leads) and secondly they have proven to be valuable tools for examining cellular processes and identifying targets in signal transduction pathways. However, besides this enormous potential of natural products, obstacles exist. These are mainly due to difficulties in isolation and/or synthesis in sufficient quantities and, consequently, to a lack of thorough investigations concerning their molecular mechanisms of action and their targets. Thus, the potential of natural products in pharmaceutical sciences is not yet fully exploited.
This Research Group (RG) will meet this challenge by exemplarily focusing on natural products from myxobacteria: 1) novel species of myxobacteria will be identified and screened for bioactive compounds. 2) innovative biotechnological/ (bio)synthetic approaches will be used to guarantee compound supply as well as create analogs of them. 3) Innovative in silico approaches will help to define the mode of action of the natural compounds, and to design more potent analogs. 4) By combining chemistry with proteomics yet unknown targets of the natural compounds shall be identified. 5) Finally, with regard to anticancer pharmacology of the myxobacterial compounds the Research Group aims at attractive and promising avenues: We will not only focus on tumor death inducing effects of compounds, but also examine their influence on tumor cell migration as well as on cancer immunosurveillance and their underlying signaling pathways. Moreover, besides tumor cells, vascular cells and immune cells known to play a role in cancer survival are in the center of interest for respective pharmacological work. To this end complex cellular and in vivo systems as well as pharmacogenomics are employed for first line characterization of promising compounds.
Bringing together scientists with strong expertise in the field of biotechnology of myxobacteria, pharmaceutical and natural product science, this Research Group will be a very important instrument for the support of “Drug Discovery from Nature”.
- Microbial Natural Products - Prof. Dr. Rolf Müller
DFG - German Research Foundation