Gramicidin A | Encyclopeptide

Chemical Identity

Property	Value
Chemical Formula	C99H140N20O17
Molecular Weight	1882 Da
CAS Number	11030-57-4
Peptide Class	Linear Pentadecapeptide
Sequence	VGALAVVVWLWLWLW-NH2 (alternating D/L)
Origin	Aneurinibacillus migulanus

Structure

Gramicidin A is a linear pentadecapeptide with alternating D- and L-amino acids, a formyl group at the N-terminus, and an ethanolamine at the C-terminus. The alternating chirality enables the peptide to fold into a beta-helical conformation that spans lipid bilayers as a dimer, forming a cation-selective channel.

Mechanism of Action

Gramicidin A dimerizes head-to-head across lipid bilayers, forming a single-stranded beta-helix channel (4 Å diameter) that conducts monovalent cations (Na+, K+, H+, Cs+). The channel disrupts ionic gradients, causing membrane depolarization and loss of osmotic balance, leading to bacterial cell death.

Clinical Applications

Topical antimicrobial: Component of Polysporin, Neosporin
Ophthalmic infections: With polymyxin B (Polysporin ophthalmic)
Research tool: Ion channel biophysics studies
Model system: Membrane peptide interactions

Pharmacokinetics

Route: Topical, ophthalmic only
Systemic absorption: Negligible
Limitation: Too toxic for systemic use (hemolysis, neurotoxicity)
Duration: Local antimicrobial effect

Safety and Side Effects

Local irritation, contact dermatitis, and delayed wound healing at high concentrations. Systemic use would cause hemolysis, neurotoxicity, and death. Topical use is safe and well-tolerated.

References

Hladky, S.B., & Haydon, D.A. (1970). Discreteness of conductance change in gramicidin A channels. Nature, 225, 451-453.
Wallace, B.A. (1998). Recent advances in the high resolution structures of bacterial channels. Journal of Structural Biology, 121, 123-141.