Antimicrobial Peptides - Bioorthogonal Editing and Structure Determination

The increasing number of bacteria resistant against antibiotics is leading to the urgent need to discover new pharmaceuticals to fight drug-resistant pathogens. Ribosomally synthesized and post-translationally modified antimicrobial peptides (RiPPs) are a promising new class of antibiotics, as they often show high activity and, up to date, no resistance has been reported. Nevertheless, clinical application of RiPPs is often hampered by several issues, for example poor pharmacokinetics, low water solubility, as well as poor oral bioavailability. In order to improve these properties and fine tune their activity and selectivity semi-synthetic approaches are becoming popular. The aim of this thesis was to develop new bioorthogonal chemical editing of RiPPs, together with characterization and structure determination of novel peptides. To achieve the selective modification of antimicrobial peptides the peculiar reactivity of dehydroamino acids (Dha and Dhb), a common feature in RiPPs, was exploited.