Shortened cecropin A-melittin hybrids. Significant size reduction retains potent antibiotic activity.
We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15-residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes.
Andreu
D
D
Department of Organic Chemistry, University of Barcelona, Spain.
Ubach
J
J
Boman
A
A
Wåhlin
B
B
Wade
D
D
Merrifield
R B
RB
Boman
H G
HG
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects; D007301:Insect Hormones / Q000494:pharmacology*; D008555:Melitten / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000187:drug effects / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D011487:Protein Conformation
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D007301:Insect Hormones; D009842:Oligopeptides; C513873:antimicrobial hybrid peptide CM15; D008555:Melitten; C031161:cecropin A