Four sets of compounds were designed, with the first being a set of control compounds including Sanguinamide A itself and the improved Danamide F (Fig. ). A negative control homodetic peptide was added, where the thiazole is replaced with the cysteine it is derived from during biosynthesis. In the other sets, we replaced the thiazole with either pyridine, pyridine N-oxide, or benzene, to study the effect of the polarity of the aromatic group (Fig. ). In Sanguinamide A, the thiazole group is directly connected to the α-carbon of the leucine residue next to it. To facilitate a more straightforward synthesis, we decided to introduce an extra amide in this place, so that the aromatic group could be easily coupled to the leucine residue. Set B has the amine and carbonyl groups directly connected to the aryl functionality, but in the other sets an extra methylene was added to the amine side of the ring (set B) or the carbonyl (set C). Sets B and C are more flexible than set A and therefore serve to study the effect of this property. Although the amide facilitates synthesis, it does introduce an extra hydrogen bond donor which could affect the membrane permeability.