Gramicidin, also called gramicidin D, is a mix of ionophoricantibiotics, gramicidin A, B and C, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2 isoforms, so the mix has 6 different types of gramicidin molecules. They can be extracted from Brevibacillus brevis soil bacteria. Gramicidins are linear peptides with 15 amino acids.[2] This is in contrast to unrelated gramicidin S, which is a cyclic peptide.
Gramicidins are used in medicinal lozenges for sore throat and in topical medicines to treat infected wounds. Gramicidins are often mixed with other antibiotics like tyrocidine and antiseptics.[4] Gramicidins are also used in eye drops for bacterial eye infections. In drops, they are often mixed with other antibiotics like polymyxin Borneomycin. Multiple antibiotics increase efficiency against various strains of bacteria.[5] Such eye-drops are also used to treat eye infections of animals, like horses.[6]
In 1939, René Dubos isolated the substance tyrothricin.[7][8] Later this was shown to be a mix of gramicidin and tyrocidine. These were the first antibiotics to be manufactured commercially.[8] Letter "D" in gramicidin D is short for "Dubos",[9] and was invented to differentiate the mix from gramicidin S.[10]
In 1964, the sequence of gramicidin A was determined by Reinhard Sarges and Bernhad Witkop.[11][12]
In 1971, the dimeric head-to-head structure of gramicidins was proposed by D. W. Urry.[13]
Y is L-tryptophan in gramicidin A, L-phenylalanine in B and L-tyrosine in C. X determines isoform. X is L-valine or L-isoleucine – in natural gramicidin mixes of A, B and C, about 5% of the total gramicidins are isoleucine isoforms.[2]
Gramicidin helices. Antiparallel (left) and parallel double helices and the helix dimer present in lipid bilayers. C and N are C- and N-terminals.[12]
Gramicidins form helices. The alternating pattern of D- and L-amino acids is important for the formation of these structures. Helices occur most often as head-to-head dimers. 2 gramicidins can also form antiparallel or parallel double helices, especially in organic solvents. Dimers are long enough to span cellular lipid bilayers and thus function as ion channel -type of ionophores.[12]
Gramicidins can be used as topical antibiotic medications in low doses, even though they are potentially lethal for human cells. Bacteria die at lower gramicidin concentrations than human cells.[3] Gramicidins are not used internally, as their significant intake may cause hemolysis and be toxic to the liver, kidney, meninges and olfactory system among other effects.[16]
^Sarges R, Bernhard W (1964). "gramicidin A. IV. Primary sequence of valine and isoleucine gramicidin A". Journal of the American Chemical Society. 86 (9): 1862–1863. doi:10.1021/ja01063a049. ISSN0002-7863.
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