The synthesis, biological activities and membrane permeability of gramicidin S (GS) analogs containing (Z)-(b-3-pyridyl)-a,b-dehydroalanine (DZ3Pal) residues are described. The cationic side chains of the Orn and DZ3Pal4,40 residues in [DZ3Pal4,40 ]GS (1) are important for dissociating antimicrobial and hemolytic activity.