RETRO AND RETROENANTIO ANALOGS OF CECROPIN MELITTIN HYBRIDS

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent a ntibacterial peptides, have been synthesized. To understand the struct ural requirements for this antibacterial activity, we have also synthe sized the enantio, retro, and retroenantio isomers of two of the hybri ds and their N-terminally acetylated derivatives. All analogs of CA(1- 13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9) -NH2 were active against four strains, while two strains were resistan t to the retro and retroenantio analogs containing free NH3+ end group s, but acetylation restored activity against one of them. From these d ata it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, bot h needed to be conserved.