Lay summary
This research aims to develop novel leads as anticancer/ antibacterial therapeutics using small proteins which bind to DNA replication, repair enzymes, and prevent bacteria or cancer cells from growing. Existing anticancer/ antibiotic drugs which target these enzymes have problems with bioavailability (not getting to the right place), off-target toxicity (inhibiting the wrong thing) and the bacteria or cancer cells evolving resistance. We will engineer small proteins that tightly bind the flexible ‘switch’ regions in DNA replication enzymes; jamming them will prevent their function. We expect these novel inhibitors will be more specific and lead to better eventual drugs. We will test this on essential DNA repair and replication enzymes from the bacterium that cause gonorrhoea, and against cancer cells.