Fighting bacterial drug resistance by targeting peptidoglycan biosynthesis: Depsipeptide antibiotics and biological probes

Bacteria have an amazing ability to rapidly evolve causing an enormous problem of antibiotic resistance. Currently, all drugs on the market which show some level of bacterial resistance. For this reason among many others, new treatments are urgently needed to help those infected with these resistant bugs. One area of hope is the synthesis and study of new molecular structures capable of unique mechanisms of action to kill bacteria. The depsipeptide antibiotics lysobactin and WAP-8294A2 represent two such structures with promising activity and low resistance profiles. Both of these compounds act by targeting the peptidoglycan layer of the bacterial cell wall. By detailing efficient routes for the synthesis of these antibiotics as well as studying key structural features and biological activities, vital new insights into their function have been revealed. Furthermore, new probes have been developed which take advantage of enzymes involved in peptidoglycan biosynthesis to track the growth of this macromolecular structure in real time.