was determined using a Heλios β UV/VISspectrophotometer at λ 300 nm. Solvents were removed by rotary evaporation under reduced pressure at 40 °C. Melting points were determined using a Büchi melting point apparatus accordig to dr. Tottoli and were uncorrected.

This report describes the design, synthesis, and biochemical evaluation of alkene‐ and alkane‐bridged AB(C)‐ring mimics of the lantibiotic nisin. Nisin belongs to a class of natural antimicrobial peptides, and has a unique mode of action: its AB(C)‐ring system binds to the pyrophosphate moiety of lipid II. This mode of action was the rationale for the design of smaller nisin‐derived peptides to obtain novel potential antibiotics. As a conformational constraint the thioether bridge was mimicked by an alkene‐ or alkane isostere. The peptides of the linear individual ring precursors were synthesized on solid support or in solution, and cyclized by ring‐closing metathesis in solution with overall yields of between 36 and 89 %. The individual alkene‐bridged macrocycles were assembled in solution by using carbodiimide‐based synthesis protocols for the corresponding AB(C)‐ring mimics. These compounds were tested for their binding affinity toward lipid II by evaluation of their potency to inhibit nisin‐induced carboxyfluorescein release from large unilamellar vesicles. It was found that these AB(C)‐ring mimics were not able to induce membrane leakage; however, they acted by inhibiting nisin‐induced carboxyfluorescein release; this indicates their affinity toward lipid II. These results imply that an alkene or alkane moiety is a suitable thioether bridge mimic.

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