Title: Rescuing the last line lipopeptide antibiotics, the polymyxins
As efforts in antibacterial drug discovery dwindle due to pharma’s perception of a non-profitable model and bacteria constantly evolving to resist frontline antibiotics, we now face the real prospect of common, treatable infections becoming fatal. Many have rekindled the “golden age” of antibiotics and have pursued novel chemical modifications of those from that era. The polymyxins are a family of potent Gram-negative lipopeptides that were gradually withdrawn from the clinic in the late 1960s due to ongoing toxicity issues. In this talk I will present our approach to generate a novel class of S-lipidated polymyxin analogues using our cysteine-lipidation ClipPA chemistry and discuss their activity against Gram-negative bacteria and their improved toxicity profiles.