SYSCHEMBIOL · Systems Chemical Biology - Chemical Biological Perturbation and Dissection of Dynamic Biological Systems

In Systems Chemical Biology research small drug-like molecules are employed to analyze the construction, wiring and spatiotemporal regulation of protein networks in dynamic biological systems. They act fast, reversibly, conditional, do not alter network architecture and need to be biologically relevant, a property particularly given for the scaffolds of natural product classes chosen in evolution to interact with proteins and to modulate dynamic biological systems.In the research project novel cheminformatic methods will be developed to analyse all known natural products and additional biologically relevant compound classes and to identify natural product fragments in order to guide the synthesis of natural product-inspired compound collections each of ca. 500-1000 members with high scaffold diversity (in particular indoles, spirooxidoles, tetrahydropyrans, iridoids, lactones, hybrid natural products). The synthesis will include the development of novel organic synthesis methodology with a special emphasis on enantioselective catalysis and multi-step Domino sequences. The compound collection will be screened in unbiased phenotypic assays monitoring mitosis and dynamic signal transduction pathways. The patterns of cellular targets of hit compounds will be identified and validated by means of chemical proteomics, biochemistry, biophysics and cell biology investigations, and novel chemical probes for the study of dynamic biological processes and systems will be devised.Systems Chemical Biology research will have a major impact on basic science by opening up unprecedented opportunities for the study of dynamic biological systems enabling breakthrough discoveries, and it will create a novel systematic means to identify drug candidates that target multiple proteins.