Cecropin

Cecropin A contains two alpha-helical segments separated by a short hinge region. The N-terminal helix is amphipathic and cationic, providing electrostatic targeting to bacterial membranes. Upon contact, cecropins adopt their helical conformation and insert into the bilayer through a mechanism involving initial electrostatic binding followed by hydrophobic insertion. At higher concentrations, they form pores through a barrel-stave mechanism; at lower concentrations, carpet-model disruption predominates. Gram-positive and Gram-negative bacteria are both targeted.

Cecropin A lacks hemolytic activity while melittin is a potent membrane disruptor but highly hemolytic. Hybrid peptides (CA(1-7)M(2-9), CAMA) combining the N-terminal domain of cecropin with the active core of melittin exhibit synergistic antimicrobial potency without the hemolytic toxicity of melittin. These hybrids have become important models for studying AMP design and the relationship between membrane selectivity and cell-type discrimination.

Cecropins show low MIC values (0.5-5 uM) against E. coli, Salmonella, Pseudomonas, and Staphylococcus species without detectable hemolytic activity up to 100 uM. Cecropin P1 from porcine intestine provides evidence for cecropin-type peptides in mammals. Plant expression of cecropin genes confers bacterial resistance to transgenic crops, demonstrating efficacy in vivo.

Cecropin A and hybrid peptides selectively kill cancer cell lines including leukemia, bladder cancer, and melanoma cells at concentrations that spare normal lymphocytes. The selectivity mechanism parallels other AMPs, phosphatidylserine exposure on cancer cell surfaces. Cecropin-KLAKLAK hybrid peptides targeting mitochondrial membranes have shown enhanced anticancer potency.