The unique antibacterial properties and structural complexity of the lantibiotics has stimulated considerable interest in the development of methodology to synthesise these peptides. One of the most challenging issues has been the synthesis of polycyclic peptides with multiple thioether bridges between side-chains, which are a characteristic feature of the lantibiotics. In this perspective, the different approaches to this problem, including solution-phase synthesis, solid-phase synthesis, biomimetic approaches and biotransformation strategies, are reviewed, highlighting the advances resulting from each of these approaches.
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