Antibiotics

Antibiotic Mode of Action/Resistance

The biggest threats to the continued use of β-lactam antibiotics, including the penicillins and cephalosporins, is that of bacterial resistance. In collaboration with partners in the European Intafar Project we are presently investigating new types of antibiotic that target penicillin binding proteins that are resistant to β-lactams such as penicillins. We are also working on the design and synthesis of inhibitors for the metallo β-lactamases - there are no clinically used inhibitor of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.

Our projects involve close collaboration between synthetic chemists, structural biologists/ modelers and biologists. Current research includes new template identification using high throughput screening, structure- and fragment- based design, inhibitor synthesis based on in silico results, and the synthesis of analogues and derivatives of natural product based antibiotics.

In recent work we have investigated the mechanism of action of Lactivicin, the only naturally occuring non β-lactam compound to target penicillin binding proteins, by synthesising analogues and carrying out crystallographic studies. Derivatives of Lactivicin show promise against penicillin resistant strains. We have also been developing new types of penicillin binding protein inhibitor, that bind irreversibly, with a particular focus being on boronic acids.