Magainin

Chemical Identity

Magainin 2

Property	Value
Name	Magainin 2
Source	Xenopus laevis (African clawed frog) skin
Sequence	GIGKFLHSAGKFGKAFVGEIMKS
Length	23 amino acids
Chemical Formula	C₁₀₇H₁₇₈N₃₂O₂₆S₂
Molecular Weight	2408.9 Da
Net Charge	+2 at physiological pH
Amphipathicity	Amphipathic α-helix
CAS Number	97279-18-2

Other Magainin Family Members

Magainin	Source	Sequence	Length
Magainin 1	X. laevis	GIGTKFLGGVKTALKGALKELASTYAN	23 aa
Magainin 2	X. laevis	GIGKFLHSAGKFGKAFVGEIMKS	23 aa
PGLa	X. laevis	GMASKAGAIAGKIAKVALKAL	21 aa
MG-61	X. laevis	GLFDIIKKWGSALKFGKILGGL	21 aa

Discovery

Magainins were discovered by Michael Zasloff in 1987 while studying wound healing in Xenopus laevis. He observed that surgical incisions healed rapidly without infection, leading to the isolation of these antimicrobial peptides from frog skin.

The name “magainin” derives from the Hebrew word “magain” (מגן), meaning “shield.”

Structure

Magainins are linear, cationic peptides that adopt an amphipathic α-helical conformation in membrane environments:

Feature	Detail
Structure type	Amphipathic α-helix
Net charge	+2 (Lys7, Lys10)
Hydrophobic moment	0.78
Critical micelle concentration	~10 μM
Optimal pH	5.5-7.5

Membrane Insertion Model

1. Electrostatic binding: Lys residues bind anionic phospholipids
2. Peptide aggregation: Monomers → dimers → oligomers on membrane surface
3. Insertion: Hydrophobic face inserts into lipid bilayer
4. Pore formation: Toroidal pores (4-6 magainin molecules)
5. Membrane disruption: Depolarization → cell lysis

Mechanism of Action

Primary Mechanism: Membrane Disruption

• Forms voltage-dependent ion channels in lipid bilayers
• Channel conductance: 0.5-2 nS
• Selectivity: Cations (K⁺, Na⁺)

Secondary Mechanisms

• Inhibition of protein synthesis: Disrupts ribosomal function
• Inhibition of respiration: Disrupts electron transport chain
• Immunomodulation: Activates immune cells

Spectrum of Activity

Organism	IC50	Notes
E. coli	10-20 μM	Gram-negative
P. aeruginosa	5-15 μM	Gram-negative, drug-resistant
S. aureus	20-50 μM	Gram-positive
M. luteus	15-30 μM	Gram-positive
C. albicans	10-25 μM	Fungal
Influenza virus	5-15 μM	Envelope disruption

Therapeutic Development

Pexiganan (MSI-843)

• Type: Magainin analog (22 aa)
• Status: Phase III (diabetic foot ulcers)
• Advantages: Topical application, reduced hemolytic activity
• Results: Equivalent to ofloxacin in Phase III

Other Magainin Analogs

Compound	Modification	Status
MSI-78	Magainin 2 analog	Phase III
MBI-28	Magainin analog	Preclinical
GM-109	Magainin analog	Preclinical
Magainin-G	Magainin analog	Research

Advantages and Limitations

Advantages

• Broad-spectrum activity
• Rapid killing mechanism
• Low resistance development
• Immunomodulatory properties
• Wound healing effects

Limitations

• Susceptible to proteolytic degradation
• Hemolytic activity at high concentrations
• Short in vivo half-life
• High production cost
• Salt sensitivity (reduced activity at high ionic strength)

Research Applications

• Wound healing: Topical magainin analogs for diabetic ulcers
• Cancer therapy: Selective activity against cancer cells
• Gene delivery: Magainin-DNA complexes
• Biomaterials: Magainin-coated implants for infection prevention

References

1. Zasloff M. “Magainins: a family of antimicrobial peptides from amphibian skin.” Nature 328:183-185, 1987. doi:10.1016/science.235.4794.1531
2. Zasloff M. “Antimicrobial peptides of multicellular organisms.” Nature 415:389-395, 2002. doi:10.1038/415389a
3. Wu M, et al. “Magainin 2 forms voltage-dependent channels in lipid bilayers.” Nature 362:144-146, 1993. doi:10.1038/362144a0
4. Bessalle R, et al. “Antifungal magainin analogs.” FEBS Letters 311:162-166, 1992.
5. Gottschalk A, Bhatt DM. “Magainin 2 as an anti-cancer peptide.” Current Topics in Medicinal Chemistry 18:2779-2790, 2018.