NMR studies revealed two major structural differences between the lead peptide 15c and its parent peptides p3 and p1 (the latter exhibiting higher hemolytic activity): (1) 15c exhibited the lowest tendency to aggregate in water, and (2) it maintained the highest backbone stability. In contrast, parent peptide p1 formed high-order oligomers or aggregates in water at concentrations above 0.15 mM due to its extensive continuous hydrophobic surface.