Abstract
Melittin is a good model antimicrobial peptide to understand the basis of its lytic activities against bacteria and mammalian cells. Novel analogues of melittin were designed by substituting the leucine residue(s) at the "d" and "a" positions of its previously identified leucine zipper motif. A scrambled peptide having the same composition of melittin with altered leucine zipper sequence was also designed. The analogues of melittin including the scrambled peptide showed a drastic reduction in cytotoxicity though they exhibited comparable bactericidal activities. Only melittin but not its analogues localized strongly onto hRBCs and formed pores of similar to 2.2-3.4 nm. However, melittin and its analogues localized similarly onto Escherichia coli and formed pores of varying sizes as tested onto Bacillus megaterium. The data showed that the substitution of hydrophobic leucine residue(s) by lesser hydrophobic alanine residue(s) in the leucine zipper sequence of melittin disturbed its pore-forming activity and mechanism only in hRBCs but not in the tested bacteria.