Gramicidin D | Encyclopeptide

Chemical Identity

Property	Value
Molecular Weight	~1880 Da (mixture)
CAS Number	1405-97-6
Peptide Class	Linear Pentadecapeptide
Components	Gramicidins A, B, C
Origin	Aneurinibacillus migulanus

Structure

Gramicidin D is a naturally occurring mixture of gramicidins A (80%), B (5%), and C (15%). These are linear pentadecapeptides with alternating D- and L-amino acids, an ethanolamine at the C-terminus, and a formyl group at the N-terminus. Gramicidin A contains Trp at position 11, B contains Phe, and C contains Tyr.

Mechanism of Action

Gramicidin peptides dimerize to form beta-helical ion channels spanning the lipid bilayer. These channels selectively conduct monovalent cations (Na+, K+, H+), disrupting transmembrane electrochemical gradients. The channel formation causes loss of ionic homeostasis and cell death in susceptible bacteria.

Clinical Applications

Topical infections: Wound infections, skin infections (in combination with other agents)
Ophthalmic infections: Gram-positive conjunctivitis (with polymyxin B)
Throat infections: Lozenges (as tyrothricin component)
Not for systemic use: Too hemolytic and toxic for parenteral administration

Pharmacokinetics

Route: Topical, ophthalmic, throat only
Systemic absorption: Negligible with topical use
Limitation: Cannot be administered systemically

Safety and Side Effects

Local irritation, contact dermatitis, and delayed wound healing. Systemic administration would cause hemolysis, neurotoxicity, and renal failure. Topical use is generally well-tolerated.

References

Dubos, R.J. (1939). Studies on a bactericidal agent from soil Bacillus. Journal of Experimental Medicine, 70, 1-10.
Wallace, B.A. (2000). Gramicidin channels. Annual Review of Biophysics and Biomolecular Structure, 29, 365-390.