The main research theme is concerned with the study of protein epitope mimetics - synthetic molecules designed to have folded structures that mimic the biologically important surface features of proteins. We use synthetic chemistry to synthesize peptidomimetics, study their preferred structures in solution, often using NMR spectroscopy, and investigate their biological activity either using assays developed in-house, or through collaborations with external research groups. We explore potential applications of these mimetics as novel drugs and vaccines targeting important areas of unmet medical need, and work together with industry to develop potential clinical candidates.
The projects include:
- the discovery and mechanism of action of a new family of antibiotics that target outer membrane (OM) biogenesis in Gram-negative bacteria. These antibiotics have folded ß-hairpin structures, which are used to target essential ß-barrel OM proteins in important human bacterial pathogens, such as Pseudomonas aeruginosa. Already one new clinical candidate has been developed in collaboration with Polyphor AG, which is now in clinical trials in hospital patients to treat infections caused by P. aeruginosa.
- the development of novel synthetic vaccine candidates against HIV-1. Here 3D structural information on the HIV-1 envelope spike is being used to design epitope mimetics. This project is in collaboration with the Institute of Medical Virology at UZH.
- the development of novel synthetic vaccine candidates against the malaria parasite Plasmodium falciparum. This project is in collaboration with the Swiss Tropical and Public Health Institute in Basel. Already two components of a potential malaria vaccine have been developed and tested in clinical trials in Europe and Africa. In ongoing work, additional new components for this malaria vaccine are being developed, to improve the promising levels of protection already seen in these earlier trials.