“…Variants of nukacin ISK-1, lacticin 481, and bovicin HJ50 have been investigated for bioactivity (Figure ). ,− As first shown for mersacidin, the highly conserved Glu/Asp in the ring C lipid II binding motif (A-ring for lacticin/nukacin/bovicin) is essential for bioactivity in all investigated compounds. ,, In addition, Lys residues in these compounds are important for bioactivity, possibly by increasing the affinity for the negatively charged lipids in the bacterial membrane. ,,, Disruption of any of the rings in bovicin HJ50, including the macrocycle generated by disulfide formation, resulted in complete loss of bioactivity . The importance of these rings was also reported for lacticin 481, and synthetic studies showed that the stereochemistry of the three (Me)Lan cross-links is also critical for bioactivity.…”