Antibiotics against Gram-negative pathogens

Because of the constant development of resistences against antibiotics against pathogenic bacteria there is an urgent demand for novel antibiotics. Due to the structure of the Gram-negative bacterial cell wall these bacteria pose a special challenge for drug development.
The architecture of the cell wall makes diffusion of small molecules across the membrane difficult compared to Gram-positive bacteria and eukaryotes. Specific defense mechanisms like efflux pumps make this task even more aggrevating.

The group focusses on development of novel drugs agains Gram-negative pathogens as well as the investigation of structure-transport relationships between chemical strcuture and bacterial uptake. The latter shall also pave the way for easier development of new antibiotic classes or broadening the biological spectra of the existing ones.

Many natural products have been optimized for their antibiotic properties by nature. The synthesis and semisynthesis of such natural products thus composes a major focus of the group.
In order to allow the application of such compounds in humans the modification of such structures is usually inevitable, since specific pharmaceutical parameters of the compounds have to be adjusted and the chemical structure often has to be simplified for commercialisation. Lead structure optimisation for drug like properties, e.g. by taking things like physicochemical properties, eADME and bacterial specific parameters like frequency of resistence into account, is thus another major group focus.