Anisomycin

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Anisomycin[1]
Anisomycin structure.png
Identifiers
CAS number 22862-76-6 N
PubChem 31549
ChemSpider 29260 YesY
UNII 6C74YM2NGI YesY
ChEBI CHEBI:338412 N
ChEMBL CHEMBL423192 N
Jmol-3D images Image 1
Properties
Molecular formula C14H19NO4
Molar mass 265.31 g/mol
Melting point 139-143 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Anisomycin, also known as flagecidin is an antibiotic produced by Streptomyces griseolus which inhibits protein synthesis. Partial inhibition of DNA synthesis occurs at anisomycin concentrations that effect 95% inhibition of protein synthesis.[2] Anisomycin can activate stress-activated protein kinases, MAP kinase and other signal transduction pathways.

Anisomycin is inactive against bacteria.

Pharmacology[edit]

Anisomycin interferes with protein and DNA synthesis by inhibiting peptidyl transferase or the 80S ribosome system.

Anisomycin is also mentioned as a potential psychiatric drug, as it may inhibit the consolidation of new context-specific long-term memories.".[3]

Injection of anisomycin into the hippocampus has been proposed for selective removal of memories.[4]

Biosynthesis[edit]

Despite anisomycin's wide usage as a protein biosynthesis inhibitor, there have been few studies centered around the biosynthesis of anisomycin. One study by Butler in 1965 proposed possible precursors to this natural product. Fermentation of Streptomyces with labeled amino acids was followed by a degradation of the radioactive anisomycin and deacetylanisomycin products to determine the locations of the labeled carbons. Although its pyrrolidine-based structure suggests that it is derived from proline, the results from the experiments indicated that tyrosine, glycine, methionine, and acetate are the primary precursors for the biosynthesis of anisomycin. Tyrosine and, to a limited degree, phenylalanine, contribute to C-2 of the pyrrolidine ring. Methionine is likely responsible for the methylation of the hydroxyl group on the aromatic ring as S-adenosylmethionine (SAM). Glycine or acetate account for C-4 and C-5 on the pyrrolidine ring. It was noted that deacetylanisomycin was a prominent product in the first few days of fermentation, suggesting that acetylation of the C-3 hydroxyl group by acetyl Co-A is the final step in the biosynthesis of anisomycin. The source of the nitrogen within the ring and C-3 were undetermined. However, C-3 is not likely to be provided by the carboxylic acid group of tyrosine because tracking of radioactivity indicated that tyrosine undergoes decarboxylation during fermentation.[5]

Anisomycin biosynthesis.gif

Other uses[edit]

Anisomycin is used as a component of Martin Lewis agar, an in vitro diagnostic product which is used extensively in the United States for the selective isolation of Neisseria gonorrhoeae and Neisseria meningitidis.[1]

See also[edit]

References[edit]

  1. ^ a b Anisomycin from Sigma Aldrich
  2. ^ Grollman, Arthur P. (1967). "Inhibitors of protein biosynthesis. II. Mode of action of anisomycin". The Journal of Biological Chemistry 242 (13): 3226–33. PMID 6027796. 
  3. ^ Barrientos, Ruth M; O'Reilly, Randall C; Rudy, Jerry W (2002). "Memory for context is impaired by injecting anisomycin into dorsal hippocampus following context exploration". Behavioural Brain Research 134 (1–2): 299–306. doi:10.1016/S0166-4328(02)00045-1. PMID 12191817. 
  4. ^ Wang, S.-H.; Ostlund, SB; Nader, K; Balleine, BW (2005). "Consolidation and Reconsolidation of Incentive Learning in the Amygdala". Journal of Neuroscience 25 (4): 830–5. doi:10.1523/JNEUROSCI.4716-04.2005. PMID 15673662. 
  5. ^ Butler, K. (1966). "Anisomycin. II.1 Biosynthesis of Anisomycin". The Journal of Organic Chemistry 31 (1): 317–20. doi:10.1021/jo01339a503. PMID 5900818.