Structure-based design of novel anti-bacterial drugs
Antibiotic resistance represents a major and escalating public health concern. There is, therefore, a pressing need to develop new drugs that combat bacterial disease in ways that are not susceptible to current bacterial resistance mechanisms. In this project you will use structure-based methods to design, synthesise and evaluate inhibitors of the bacterial enzyme DsbA. DsbA enzymes from Gram-negative bacteria have been shown to be essential mediators of bacterial virulence. Therefore inhibitors of DsbA have the potential to act as antivirulence agents We have previously undertaken a fragment-based screen to identify compounds that bind to and inhibit DsbA. In this project you will elaborate these to generate potent and specific inhibitors of DsbA. These will be evaluated for their ability to inhibit virulence in clinical strains of bacteria.