New target

Step beyond current understanding of drug discovery

Our group is working to enhance the scope of "classical" drug discovery. We are focused on discovering and validating new targets explore unique chemical space, develop new computational means for virtual screening. Novel, sometimes unexpected, treatment strategies must be validated carefully. To achieve this, we build highly efficient pipeline merging structural biology, medicinal chemistry and computational modelling and simulation to quickly obtain molecular probe, able to prove (or disprove) our new targets. We have validated this strategy by developing unique mode of action molecules targeting glycosomal transport (Dawidowski M. et al. Science 2017).

Transport mechanisms in health and disease

With a help of small molecule probes and protein vectors we investigate significance of transport mechanisms. Peroxisomal transport inhibitors proved to be excellent strategy to kill trypanosoma parasites. Now, we analyze opportunities provided by peroxisomal transport blockage in other parasites and mammalian cells. We also optimize our molecules towards better pharmacological profile. To support our activities we were awarded BMBF VIP+ funding (expected to start October 2018). In this work we are partnering with the group of Professor Ralf Erdmann from Ruhr University Bochum.

Not only peroxisomal transport is investigated. We also study possibilities of using bacterial toxin fragments as vectors to carry large cargo to the cells. In this work we use unique technology to monitor cell binding and internalization of cargo provided by Ridgeview Instruments, Uppsala. This project is realized in cooperation with Jagiellonian University, Cracow.

Antibiotic resistance – fragments against arising threat

Beta-lactam antibiotics are most important defense line against bacterial infections. They not only cure but also shield patients with weakened immune systems, after surgeries etc. Very fast spreading of antibiotic resistance genes among pathogenic bacteria is a very serious threat to public health. We have used an NMR-based fragment screening approach to find inhibitors of beta-lactamases. The molecules proved to have excellent activity in vitro and in bacterial MIC assays. We have solved X-ray structures of lactamases in complex with our inhibitors and use medicinal chemistry approach to optimize them further. Simultaneously, we use beta-lactamases as a model system for fragment-based NMR techniques development.