Molecular Tools for the Life Sciences

The vast amount of data originating from the different genome initiatives in the context of systems biology requires more and more emphasis to be placed on the elucidation of dynamic processes present in the living cell on the functional level. Synthetic tailor-made probes have been proven to facilitate this analysis.

Systematic analysis of the proteins expressed by a cell at a certain time and under certain condition with designed molecules (Functional Proteomics) is of eminent importance. Moreover, Chemical Genomics is a powerful strategy to evaluate the influence of synthetic small molecules (e.g. drug candidates) on biological systems.

Previous and Current Research

Either an enrichment step or selective tagging with reporter groups (e.g. fluorescent labels, radioactive tags, or biotin) can be utilized for the generation of proteome subsets. As Sciencesseparation of protein mixtures by 2D-PAGE usually involves denaturing conditions, only such protein families could until now be tagged where irreversibly binding ligands (suicide inhibitors) were known. Irreversibly binding ligands are not available for the vast majority of proteins. We developed novel engineered chemical probes for the creation of proteome subsets of such protein families, comprising a (semi-)specific, reversibly binding protein ligand (inhibitor) linked to a reporter group and a reactive group (photoaffinity label). Small-molecule kinase inhibitors, metalloprotease inhibitors, sulfatase inhibitors, and integrin ligands, respectively, have been chemically modified to allow for family-wise

  • protein enrichment using magnetic beads or affinity chromatography
  • covalent tagging with a fluorophor or biotin using photoaffinity labelling.

Future Projects and Aims

The current projects aim at the development of novel molecular tools tailored to the elucidation of biochemical relationships. In the focus of the investigations are protein-protein and protein-drug interactions. The novel tools will not only be suitable for the detection of binding partners and protein classes in eukaryotic systems, but also in the evaluation of interactions in prokaryotes, including complex microbial systems.

Latest Publications of the Group