Gramicidin, also calledgramicidin D, is a mix ofionophoricantibiotics,gramicidin A,B andC, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2isoforms, so the mix has 6 different types of gramicidin molecules. They can be extracted fromBrevibacillus brevis soil bacteria. Gramicidins are linearpeptides with 15amino acids.[2] This is in contrast to unrelatedgramicidin S, which is a cyclic peptide.
Gramicidins are used in medicinallozenges for sore throat and in topical medicines to treat infected wounds. Gramicidins are often mixed with other antibiotics liketyrocidine andantiseptics.[4] Gramicidins are also used ineye drops for bacterial eye infections. In drops, they are often mixed with other antibiotics likepolymyxin B orneomycin. 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 substancetyrothricin.[7][8] Later this was shown to be a mix of gramicidin andtyrocidine. 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 fromgramicidin 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 determinesisoform. 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- andN-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-headdimers. 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 asion channel -type ofionophores.[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 causehemolysis and be toxic to the liver, kidney,meninges andolfactory 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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