Magainin 2
Magainin 2 is a 23-amino acid antimicrobial peptide from the skin of the African clawed frog Xenopus laevis, one of the first AMPs discovered with broad-spectrum activity.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C122H210N32O31 |
| Molecular Weight | 2622.18 g/mol |
| CAS Number | 108852-60-2 |
| IUPAC Name | Gly-Ile-Gly-Lys-Phe-Leu-His-Ser-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Gly-Glu-Ile-Met-Asn-Ser |
| Peptide Class | Antimicrobial Peptide (Amphibian) |
| Origin | Xenopus laevis (African clawed frog) |
Structure
Magainin 2 is a 23-amino acid linear, cationic, amphipathic alpha-helical peptide. It was discovered by Michael Zasloff in 1987 from the skin of the African clawed frog. The peptide contains seven positively charged residues (four lysines, one arginine, two histidines) and forms an amphipathic helix in membrane environments with charged residues on one face and hydrophobic residues on the other.
Mechanism of Action
Magainin 2 disrupts bacterial membranes through the barrel-stave or carpet mechanism:
- Membrane binding: Cationic residues bind to anionic bacterial membrane lipids
- Helix insertion: The amphipathic helix inserts perpendicularly into the membrane
- Pore formation: At sufficient concentrations, peptides oligomerize to form transmembrane pores
- Cell lysis: Ion flux through pores leads to membrane depolarization and cell death
The peptide shows selectivity for bacterial membranes over mammalian cell membranes due to the higher proportion of anionic lipids in bacterial membranes.
Biological Functions
Magainin 2 is part of the innate immune defense system of frog skin:
- Antimicrobial spectrum: Active against gram-positive and gram-negative bacteria, fungi, and some protozoa
- Low hemolytic activity: Selectivity for prokaryotic membranes over eukaryotic membranes
- Synergy: Enhanced activity when combined with other AMPs or conventional antibiotics
Clinical Relevance
Magainin 2 and its synthetic analog pexiganan (MSI-78) have been developed as topical antimicrobial agents. Pexiganan cream was investigated for diabetic foot ulcers but received a FDA complete response letter. The peptide inspired development of numerous synthetic AMPs and demonstrated that amphibian skin is a rich source of antimicrobial peptides. Structural insights from magainins have informed rational design of therapeutic AMPs.
Safety and Side Effects
Magainin 2 has low toxicity to mammalian cells at antimicrobial concentrations. Limited hemolytic activity (typically <5% at therapeutic concentrations). Rapid degradation by proteases in serum limits systemic use, confining applications to topical formulations.
References
- Zasloff, M. (1987). Magainins, a class of antimicrobial peptides from Xenopus skin. Proceedings of the National Academy of Sciences, 84, 5449-5453.
- Maloy, W.L., & Kari, U.P. (1995). Structure-activity studies on magainins and other host defense peptides. Biopolymers, 37, 105-122.
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