Lugdunin derivatives: From natural product to drug? Editing of the structure of the Lugdunin scaffold confirmed the fundamental role of the thiazolidine moiety and of the alternating stereochemistry of the D-and L-amino acids and allowed to further explore Lugdunin SAR . An alanine scan of the peptide revealed the side chains that are amenable to synthetic alterations. The most active Lugdunin derivative was obtained by introducing a second tryptophan residue . Also, increasing the hydrophobicity of Lugdunin by substituting tryptophan with naphthalene-or anthracene-alanine, resulted in active compounds . These modifications confirmed the importance of aromaticity and hydrophobicity in promoting membrane insertion, key factors that drive Lugdunin's mechanism of action.