A minimal peptide scaffold takes on Staphylococcus aureus

How small can an antibacterial peptide become while retaining useful activity? In a collaborative study, we explored ultra-short lipopeptides built around an arginine–proline–arginine core. Changing where the lipid attaches and how the linker is oriented helped identify active compounds.

One lead, compound 15, inhibited Staphylococcus aureus growth, reduced biofilm formation and was active against five clinical isolates in laboratory tests. It also showed stability in human serum. The results identify a starting scaffold for further development; effectiveness as a treatment remains to be established.

Published online in European Journal of Medicinal Chemistry on 17 March 2026. See the journal record for the article and its associated correction.