Development of truncated Battacin antimicrobials featuring novel N-terminal fatty acids with an excellent safety profile.

ABSTRACT

Octapeptin B5 peptides containing a novel fatty acids have been found to have enhanced antibacterial activity against Staphylococcus aureus and also have an excellent safety profile. Cyclic lipopeptides such as the polymyxins and battacin are potent antibacterial agents. It has been shown that truncated, non-linear, versions of these agents (e.g. octapeptin B5) can retain the activity of the more complex cyclic compounds. In this work the synthesis of Octapeptin B5 peptides containing a range of novel fatty acids is reported. Many of these lipopeptides have been found to have enhanced antibacterial activity against Staphylococcus aureus compared to Octapeptin B5 whilst also having an excellent safety profile in haemolytic and cytotoxicity assays.