Cationic amphipathic helix
α-helical structural motif of antimicrobial peptides with one cationic face and one hydrophobic face — drives selective membrane disruption.
For laboratory and research use only — not for human consumption.
The cationic amphipathic α-helix is a structural motif shared by the great majority of host-defence antimicrobial peptides (AMPs), including the human cathelicidin LL-37, the magainins, and many invertebrate AMPs. In aqueous solution these peptides are typically disordered, but on contact with negatively charged microbial membrane surfaces they fold into an α-helix in which one face of the helix presents positively charged lysine and arginine residues while the opposite face presents hydrophobic residues. This amphipathic arrangement enables selective binding to anionic bacterial outer membranes (rich in lipopolysaccharide and lipoteichoic acid) over the predominantly zwitterionic eukaryotic plasma membrane. Once embedded, the helix disrupts membrane integrity through a combination of carpet-model membrane permeabilisation, toroidal-pore formation, and lipid-phase disruption, leading to depolarisation, cytoplasmic leakage, and bacterial death. The cationic-amphipathic design also confers activity against fungi, enveloped viruses, and biofilms, and contributes to the AMP class's relatively low rate of resistance compared with conventional small-molecule antibiotics. Synthetic peptidomimetic AMPs and rationally designed cathelicidin analogues exploit the same architectural principles. LL-37's dual antimicrobial-immunomodulatory profile — including FPR2 agonism, angiogenesis promotion, and chemotaxis — emerges from this conserved structural framework.