We are developing the next generation of antibiotics by rationally designing metal-based molecules that trigger processes to kill pathogens.
The emergence of bacteria resistant to all classes of antibiotics is one of the greatest threats to human health. Estimates predict a chilling prospect of over 10 million deaths each year from drug-resistant infections by 2050 if antibiotic resistance continues to rise at the current rate.
There is little doubt that we must move beyond conventional drug discovery programs, which too often rely on minor modifications of known antibiotics to generate only marginally different “me-too drugs”. It is easy for microbes to develop resistance against these.
We use rational approaches such as fragment-based drug discovery to generate new antibiotic scaffolds, the structural ‘frame’ on which an antibiotic is built. We start by identifying small and simple molecules that can bind to a protein target of a pathogen by using a range of biophysical techniques. We then develop and refine these compounds to create molecules that bind more effectively through iterative cycles of design and chemical synthesis guided by structural analysis.
We are especially interested in generating metal-containing compounds, as metal centres can bring new features to organic scaffolds. Besides increasing shape diversity, they can bring about new, metal-specific modes of action, like ligand exchange reactions, the catalysis of chemical reactions, or the production of reactive oxygen species. We will leverage these unique features to develop next-generation antibiotics.