Gramicidin

Source: Wikipedia, the free encyclopedia.
TCDB
1.D.1
OPM superfamily65
OPM protein1grm
Gramicidin
JSmol)
Melting point229 to 230 °C (444 to 446 °F) [1]
Solubility in water0.006 mg/L[1]
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Gramicidin, also called gramicidin D, is a mix of

amino acids.[2] This is in contrast to unrelated gramicidin S
, which is a cyclic peptide.

Medical uses

Gramicidins work as antibiotics against

E. coli.[3]

Gramicidins are used in medicinal

eye drops for bacterial eye infections. In drops, they are often mixed with other antibiotics like polymyxin B or neomycin. 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]

History

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]

In 1993, the structure of the gramicidin head-to-head dimer in

solid-state NMR.[14]

Structure and chemistry

Gramicidins A, B and C are nonribosomal peptides, thus they have no genes. They consist of 15 L- and D-amino acids. Their amino acid sequence is:[2]

formyl-L-X-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-L-Trp-D-Leu-L-Y-D-Leu-L-Trp-D-Leu-L-Trp-ethanolamine

Y is L-

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]

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]

Gramicidin mixture is a crystalline solid. Its solubility in water is minimal, 6 mg/L, and it may form

hydrocarbons.[1]

Pharmacological effect

Gramicidins are

mitochondria halts mitochondrial ATP production in cells with mitochondria.[16]

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]

References

  1. ^
    OCLC 34552962
    .
  2. ^
    PMID 14670971
    .
  3. ^
    S2CID 4906040
    .
  4. PMID 30329199
    .
  5. PMID 14693766
    .
  6. ISBN 9781437708462
    .
  7. PMID 19870884
    .
  8. ^
    PMID 16528813
    .
  9. PMID 29045870
    .
  10. ^ "Gramicidin from Bacillus brevis product No. G 5002" (PDF). sigmaaldrich.com. 1997-09-06. Retrieved 2019-10-03.
  11. ISSN 0002-7863
    .
  12. ^
    doi:10.1039/C6RA13658C
    .
  13. PMID 5276779
    .
  14. PMID 7690158
    .
  15. PMID 22911866
    .
  16. ^
    PMID 28326255
    .
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