The emergence of drug-resistant strains of human pathogens such as P. aeruginosa, S. aureus or S. pneumoniae is a recognised threat to human health and urgently calls for the development of new antibacterial agents with novel modes of action. The department DDOP adopts a target-based strategy focussing on a portfolio of two types of drug targets.
The first group comprises targets which impair vital mechanisms within the bacteria and effectively kill them. One example is the enzyme DXS which plays a crucial role in the methylerythritol phosphate pathway, which is essential for the biosynthesis of universal isoprenoid precursors in many Gram-negative pathogens, but absent from humans. The second group comprises targets interfering with pathogenicity and virulence without affecting bacterial viability. These pathoblockers are believed to cause a lower rate of resistance development, whilst leaving the commensal microbiota untouched.
The Hirsch group applies a series of established hit-identification strategies, including structure- and fragment-based drug design, classical medicinal chemistry and virtual screening. In addition, pioneering of innovative protein-templated methods such as dynamic combinatorial chemistry and kinetic target-guided synthesis in terms of the scope of chemical reactions, biological targets and synergistic combinations addresses key bottlenecks. Use of established and innovative techniques to design, synthesize and profile the most promising inhibitors enables efficient subsequent multiparameter optimisation as well as elucidation of the mode of action.
Scientists in the interdisciplinary team have diverse backgrounds such as medicinal chemistry, synthetic organic chemistry, pharmacy, pharmacology, biology or biochemistry, resulting in a diverse skill set.
A current overview of the team and further information about the research group can be found on the HIPS page.