Lasso Peptides—A New Weapon Against Superbugs

The emergence of multi-drug-resistant bacteria (known as superbugs) represents one of the greatest challenges for human health and modern medicine. Due to their remarkable ability to rapidly develop resistance to currently used antibiotics, new molecular targets for bacteria and substances capable of effectively combating related infections are still being sought. Lasso (known also as lariat) peptides are an unusual subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a structurally constrained knotted fold resembling a lasso. They are synthesized by certain groups of microorganisms as a result of complex processes involving intricate structural changes leading to the formation of the lasso structure. Reproducing these processes using known peptide synthesis methods poses a major challenge for synthetic chemistry. Lasso peptides exhibit a range of bioactivities including antibacterial activity. Due to the lasso structure, the peptides are capable of binding to new molecular targets, including atypical sides of ribosomes, in relation to currently used antibiotics. Thus, creating new mechanisms that inhibit metabolic processes leading to the death of pathogenic bacteria. This feature makes lasso peptides a potential “last chance” weapon in the fight against emerging superbugs.