Characterization of Antimicrobial,Cytotoxic, andAntiendotoxin Properties of Short Peptides with Different HydrophobicAmino Acids at “a” and “d” Positions ofa Heptad Repeat Sequence.

To understand the influence of different hydrophobicamino acidsat “a” and “d” positions of a heptad repeatsequence on antimicrobial, cytotoxic, and antiendotoxin properties,four 15-residue peptides with leucine (LRP), phenylalanine (FRP),valine (VRP), and alanine (ARP) residues at these positions were designed,synthesized, and characterized. Although valine is similarly hydrophobicto leucine and phenylalanine, VRP showed significantly lesser cytotoxicitythan LRP and FRP; further, the replacement of leucines with valinesat “a” and “d” positions of melittin-heptadsdrastically reduced its cytotoxicity. However, all four peptides exhibitedsignificant antimicrobial activities that correlate well with theirinteractions with mammalian and bacterial cell membranes and the correspondinglipid vesicles. LRP most efficiently neutralized the LPS-induced pro-inflammatorymediators like NO, TNF-α, and IL-6 in macrophages followed byFRP, VRP, and ARP. The results could be useful for designing shortantimicrobial and antiendotoxin peptides with understanding the basisof their activity. [ABSTRACT FROM AUTHOR]