Gramicidin

Overview

Gramicidin was one of the first antibiotics used clinically. The clinically used mixture (gramicidin D) consists of several closely related 15-residue peptides with an unusual alternating L- and D-amino-acid sequence, which allows the molecule to adopt a β-helical conformation.

Two gramicidin molecules span the bacterial membrane head-to-head to form a channel that is selective for monovalent cations such as sodium and potassium. The resulting uncontrolled ion flux dissipates the transmembrane electrochemical gradient, halting energy-dependent processes and killing the cell. This same non-specific membrane action makes gramicidin toxic to mammalian cells and red blood cells, restricting it to topical use.

Because its mechanism is a widely studied prototype of membrane ion transport, gramicidin is also a classic model system in biophysics. The related cyclic peptide gramicidin S is a separate compound used as a topical antiseptic.

Mechanism of Action

The alternating L/D sequence lets gramicidin fold into a single-stranded β6.3 helix; two such helices join at their formyl-N termini to span the bilayer, forming a ~4 Å pore. Cations traverse in single file with associated water molecules, giving high but non-specific monovalent-cation conductance. Because the channel does not discriminate bacterial from mammalian membranes, systemic use causes haemolysis, confining gramicidin to topical formulations.