All designed cyclic membrane-active peptides have clearly amphiphilic nature, with well-defined surface regions: hydrophilic (residues 1-4) and hydrophobic (residues 5-7). As shown in our previous work , the replacement of the bulky Dip side chain with a flat aromatic Trp side chain (its surface area is approximately 15% smaller) elevates the conformational mobility and decreases the integrity of the apolar motif in peptide p3. Indeed, all Trp6containing peptides in set 2 show diminished integrity of their apolar motifs (Figure , Supporting Information), leading to increased solvent accessibility of the polar backbone atoms within residues that form the hydrophobic pattern (Table , Supporting Information).