Organic Synthesis of Tool Compounds in Chemical Biology
Our group is interested in the synthesis and identification of small molecule probes for the study of protein function - an increasingly important strategy known as “Chemical Genetics”. In this endeavour involving continuous collaboration between biologists and chemists, we pursue two different strategies. On one hand, we develop high-throughput methods for the synthesis of collections of chemical compounds (“libraries”) which are screened in phenotypic cell-based assays or against specific proteins. Efforts towards this goal have been rewarded by the identification of phosphatase inhibitors in the low micromolar range. Our second approach uses rational design of molecular probes to study the mechanism and the function of specific enzymes in their cellular environment. Another project in my research group aims at the use of transition-metal catalyzed reactions for the post-translational modification of proteins (e.g. farnesylation of Cys-side chains using palladium-allyl complexes).
The projects proposed here use small molecule probes for the investigation of the biosynthesis of phenazines and for activity based annotation of enzyme function in a complex biological system.
Laboratory know-how and infrastructureThe proposed projects will be carried out at the Institute of Organic Chemistry, TU Graz. The equipment required for the synthetic part of these projects will be provided by the institution. The labs are well equipped for the characterization of the synthesized compounds. Functional enzyme assays will be established at the institute. In-house expertise in this respect is available by other groups at the institute and can be additionally provided by our collaboration partners. Investigations of this group are mainly devoted to fundamental research.