Antillatoxin
Three-dimensional representation of antillatoxin
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Names | |
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IUPAC name
(6S,9S,14R,15R)-7,9,14-Trimethyl-13-methylidene-6-propan-2-yl-15-[(2E,4E)-4,6,6-trimethylhepta-2,4-dien-2-yl]-1-oxa-4,7,10-triazacyclopentadecane-2,5,8,11-tetrone
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Other names
ATX
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Identifiers | |
3D model (
JSmol ) |
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ChEMBL | |
ChemSpider | |
PubChem CID
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Properties | |
C28H45N3O5 | |
Molar mass | 503.674 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Antillatoxin (ATX) is a potent lipopeptide neurotoxin produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channels, which can cause cell depolarisation, NMDA-receptor overactivity, excess calcium influx and neuronal necrosis.
Sources
Antillatoxin is found in the venom of the marine
Structure
The three dimensional NMR study of this toxin showed that it consists of a tripeptide glycine-N-methylvaline-alanine, a hydroxycarboxylic acid and a 9-t-butyl-6,8-dimethyl-6,8-diene attached to the C5 atom of the cyclic peptide backbone.[2][3]
Analogs
There are three known
Synthesis
The figure below shows the first total synthesis of antillatoxin by Yokokawa et al. in 1998. (2E,4E)-2,4,6,6-Tetramethyl-2,4-heptadien-1-ol was transformed using a
Target
Antillatoxin is a sodium channel gating modifier with special efficacy in cells expressing
Changing the tert-butyl-substituted diene groups reduced toxicity, which proves that the twisted shape of these groups plays a critical role in the degree of neurotoxicity of ATX.[9]
Mode of action
Antillatoxin activates
Antillatoxin-induced cytotoxicity is thought to occur through excessive activation of NMDA receptors by increased sodium influx, leading to excess calcium influx and necrosis.[8] The exact mechanism is still unclear, as antillatoxin’s effect on the membrane potential is not sufficient to relieve the NMDA receptor block by magnesium.[10]
Aside from toxic effects, ATX seems to enhance neurite outgrowth in developing immature neurons, depending on sodium influx, NMDA receptor activity, voltage-gated calcium channels and the calmodulin-kinase pathway.[10]
Toxicity
The toxin has been implicated in cases of respiratory irritation, inflammation of the eye and severe
Morphological features of antillatoxin-induced neuronal toxicity are swelling of neuronal somata, thinning of neurites and blebbing of neurite membranes.[12]
Drug Interactions
Cytotoxicity can be blocked by noncompetitive NMDA antagonists, such as
Antillatoxin itself is an allosteric agonist for the action of batrachotoxin, and becomes even more effective when combined with brevetoxin.[13]
References
- PMID 11757852.
- ^ ISSN 0002-7863.
- ^ PMID 24522155.
- ^ PMID 11473443.
- ^ PMID 21156065.
- PMID 24430532.
- .
- ^ PMID 11416227.
- PMID 19998300.
- ^ PMID 20026674.
- ^ Dennison, W. C.; O'Neil, J. M.; Duffy, E. J.; Oliver, P. E.; Shaw, G. R. (1999). "Blooms of the cyanobacterium Lyngbya majuscula in coastal waters of Queensland, Australia". Bulletin de l'Institut Océanographique. NS19 632: 501–506. Retrieved 2015-10-12.
- ^ PMID 10482399.
- ^ PMID 24287955.
- PMID 26891306.