Gramicidin S | Encyclopeptide

Chemical Identity

Property	Value
Chemical Formula	C60H92N12O10
Molecular Weight	1141.45 Da
CAS Number	113-73-5
Peptide Class	Cyclic Depapeptide
Sequence	cyclo-(Val-Orn-Leu-D-Phe-Pro)2
Origin	Aneurinibacillus migulanus

Structure

Gramicidin S is a cyclic decapeptide with the sequence cyclo-(Val-Orn-Leu-D-Phe-Pro)2, containing two D-phenylalanine residues and two ornithine residues. The molecule adopts an amphipathic antiparallel beta-sheet structure stabilized by intramolecular hydrogen bonds, with hydrophobic and positively charged faces.

Mechanism of Action

Gramicidin S disrupts bacterial cytoplasmic membranes through its amphipathic structure. The hydrophobic face inserts into the lipid bilayer while the cationic ornithine residues interact with negatively charged phospholipids, causing membrane depolarization, increased permeability, and cell lysis.

Clinical Applications

Topical infections: Wound infections, skin infections
Ophthalmic infections: Conjunctivitis, blepharitis (in combination with polymyxin B)
Throat infections: Pharyngitis, tonsillitis
Limited systemic use: Too nephrotoxic and hemolytic for parenteral administration

Pharmacokinetics

Route: Topical, ophthalmic, throat lozenges only
Systemic absorption: Minimal with topical use
Metabolism: Rapidly inactivated if absorbed systemically
Limitation: Cannot be used systemically due to toxicity

Safety and Side Effects

Nephrotoxicity and hemolysis prevent systemic use. Topical application may cause local irritation, contact dermatitis, and delayed wound healing. Not for use in deep wounds or body cavities.

References

Gause, G.F., & Brazhnikova, M.G. (1944). Gramicidin S and its use in treatment of infected wounds. Nature, 154, 703.
Kondejewski, L.H., et al. (1999). Gramicidin S analogs. Journal of Biological Chemistry, 274, 13181-13192.