Antimalarial activity of dermaseptin S4 and of various derivatives. Synchronized cultures at the ring stage were cultured at 1% hematocrit and 2% parasitemia in the presence of increasing concentrations of dermaseptins. After 18 h of incubation, [3H]hypoxanthine was added, and cells were harvested 24 h later. The cell-associated radioactivity was determined and inhibition of growth was calculated by comparison with controls (without peptide). (A) Star, S4; empty circle, K4-S4; crossed circle, K20-S4; filled circle, K4K20-S4; empty rectangle, D4-S4; crossed rectangle, D20-S4; filled rectangle, D4D20-S4. (B) Star, S4(5–16); empty circle, S4(1–20); crossed circle, S4(1–16); filled circle, S4(1–12); empty rectangle, S4(5–28); crossed rectangle, S4(9–28); filled rectangle, S4(13–28). (C) Star, K4-S4(1–16); empty circle, K4-S4(1–16)a; filled circle, K4-S4(1–15)a; empty rectangle, K4-S4(1–13)a; filled rectangle, K4-S4(1–10)a.