Lantibiotics are a powerful class of antimicrobials but their success in clinical settings has been limited. Stability and solubility issues in combination with the significant synthetic challenge posed by the characteristic thioether ring structures have hampered our ability to exploit this class of natural products. A well-studied lantibiotic, nisin, is of interest due to its broad-spectrum activity and novel mode of action. It has been shown that rings A and B of nisin bind tightly to lipid II, a precursor for bacterial cell wall biosynthesis. The C terminus can then insert itself into the bacterial membrane to form stable pores causing cell lysis. This thesis investigates the synthesis of analogues of nisin with simplified structures that maintain good biological activity whilst improving stability, solubility and also giving easier synthetic access to compounds with nisin’s unique mode of action. Orthogonally protected lanthionine was synthesised and used in SPPS to produce novel analogues of rings A and B with improved stability. Rings A and B of wild type nisin were also obtained through digestion of a commercially available preparation. To maintain the pore forming abilities of nisin but simplify the synthetic route we have replaced the lanthionine containing C terminus with simpler, linear pore forming peptides and a peptoid and connected these to rings A and B using click chemistry. These hybrid peptides were assessed for their biological activity using a broth microdilution assay.