Innovative Chemical Diversity
Access to resources and expertise in chemistry is a key asset for the goals of this drug research initiative. Currently the initiative can use for its screening campaigns about 250.000 commercial compounds from the different collection at the institutes. On top, several additional unique sources are available:
Specially selected collections of small chemical substances with a molecular weight below 250 (so-called fragments) are available for screening with NMR- and protein crystal structure analyses to identify entry points for the development of protein ligands. Fragments with chemically conjugatable functionalities are available for dynamic ligation screen with functional assays (e.g. enzymes) to yield high-affinity inhibitors.
Natural products (NPs) are another valuable resource for innovative bioactive molecules. More than 50% of all approved medicines are NPs or derived from them. Modern genetics, high-throughput genome sequencing, new methods for chemical analysis and bioinformatics add to the classical, activity-driven and structure-determining screening of microbial extracts. The growing knowledge about NP biosynthetic pathways increasingly enables the rational modification of products and the optimization of yields. Scientists at the HZI and HIPS are involved at the forefront of this research. HZI/HIPS will contribute their renowned expertise with gliding bacteria and fungi. The targeted identification and structural characterization of new secondary metabolites as well as the rapid recognition of already known compounds is supported effectively through the ongoing creation of a comprehensive database of all so far described compounds.