Synthesis and biological activity of oxa-lacticin A2, a lantibiotic analogue with sulfur replaced by oxygen.

An oxidatively stable analogue 3 of lacticin 3147 A2 (2), wherein the sulfur atoms are replaced with oxygens, was synthesized using solution phase peptide synthesis and sequential on-resin cyclizations. Biological evaluation suggests that oxa-lacticin A2 (3) retains independent antimicrobial activity against Gram-positive bacteria but lacks the synergistic activity with natural lacticin A1 that is characteristic of the native lacticin A2 peptide.