Maitotoxin-1

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Structural formula
Structural formula of maitotoxin-1
General
Surname Maitotoxin-1
other names

MTX-1

Molecular formula C 164 H 256 Na 2 O 68 S 2
External identifiers / databases
CAS number 59392-53-9
EC number 800-521-0
ECHA InfoCard 100.227.039
PubChem 71460273
ChemSpider 25991548
Wikidata Q425072
properties
Molar mass 3425.86 g mol −1
Physical state

firmly

safety instructions
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 300-310-330
P: ?
Toxicological data

50 ng.kg −1 ( LD 50 ,  mouse ,  ip )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Maitotoxin-1 , MTX-1 for short, is one of three structurally and biochemically related marine toxins named after the Tahitian name Maito for the bristle- tooth doctor fish species Ctenochaetus striatus , in which it was discovered in 1976. A little later it was also found in some unicellular organisms living in the sea , especially the species Gambierdiscus toxicus . Fish likely ingest the poison by eating these dinoflagellates . Food poisoning due to maitotoxin-1 after consuming the corresponding fish is known as ciguatera . In biochemical and physiological research, maitotoxin-1 is used in studies of ion channels .

properties

Maitotoxin-1 as a pure substance is a colorless, amorphous solid that is readily soluble in water as well as in methanol , acetonitrile and dimethyl sulfoxide (DMSO), but is hardly or not soluble in most other organic solvents. The primary chemical structure was clarified in 1998. The molecule with a molar mass of 3425.86 Dalton (3425.86 g / mol) and the empirical formula C 164 H 256 Na 2 O 68 S 2 consists of 32 ring structures , including 28 6-rings, three 7-rings and one 8 Ring, which together with 32 ether bonds and 28 hydroxyl groups form a C 142 chain. Before the discovery of the polytheonamides , maitotoxin-1 was the largest known molecule formed by biosynthesis in a living organism that was not constructed as a polymer . The three-dimensional structure is known:

Space- filling model of maitotoxin-1

Despite its complex structure, maitotoxin-1 is heat-resistant, unlike many other animal and plant poisons. It is probably the most powerful natural poison known that is not made up of amino acids like a peptide .

effect

With a lethal dose (LD 50 ) of 50 nanograms per kilogram of body weight ip in mice, maitotoxin-1 is one of the most toxic naturally occurring substances. The toxic effect is based on the activation of calcium-permeable, non-selective cation channels in the cell membrane . This leads to a massive influx of calcium ions into the cytosol of the cells and thus a disruption of the electrolyte balance of the cells in the body. In addition, it causes smooth muscle contractions and the release of neurotransmitters .

synthesis

KC Nicolaou's working group has been working on total synthesis since 1996, although the project is currently on hold because there are problems with funding.

literature

  • T. Yasumoto: The Chemistry and Biological Function of Natural Marine Toxins. In: The Chemical Record . 1 (3) / 2001. Wiley, pp. 228-242, ISSN  1527-8999
  • Escobar LI, Salvador C., Martinez M., Vaca L.: Maitotoxin, a Cationic Channel Activator. In: Neurobiology (Bp). 6 (1 )/1998. Akadémiai Kiadó, pp. 59-74, ISSN  1216-8068
  • Yoshito Kishi : Complete Structure of Maitotoxin. In: Pure & Applied Chemistry. 70 (2 )/1998. IUPAC, pp. 339-344, ISSN  0033-4545
  • A. Yokoyama, M. Murata, Y. Oshima, T. Iwashita, T. Yasumoto: Some Chemical Properties of Maitotoxin, a Putative Calcium Channel Agonist Isolated From a Marine Dinoflagellate. In: Journal of Biochemistry (Tokyo). 104 (2) / 1988. Japanese Biochemical Society, pp. 184-187, ISSN  0021-924X
  • Michael Weiß: Pharmacology and toxicology of maitotoxin and other marine toxins (PDF file; 3.5 MB). Final thesis of the postgraduate studies in toxicology and environmental protection at the Medical Faculty of the University of Leipzig, 2001, pp. 24–30.

Individual evidence

  1. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of maitotoxin in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on August 13, 2018, is reproduced from a self-classification by the distributor .
  2. ↑ Entry on maitotoxin-1 in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on August 13, 2018.
  3. ↑ Toshiyuki Hamada, Shigeki Matsunaga, Gen Yano, Nobuhiro Fusetani: Polytheonamides A and B, Highly Cytotoxic, Linear Polypeptides with Unprecedented Structural Features, from the Marine Sponge, Theonella swinhoei . In: Journal of the American Chemical Society . tape 127 , no. 1 , 2005, p. 110–118 , doi : 10.1021 / ja045749e .
  4. ↑ Makoto Sasaki, Nobuaki Matsumori, Takahiro Maruyama, Taro Nonomura, Michio Murata, Kazuo Tachibana, Takeshi Yasumoto: The Complete Structure of Maitotoxin, Part I: Configuration of the C 1 –C 14 Side Chain . In: Angewandte Chemie International Edition . tape 35 , no. 15 , 1996, pp. 1672-1675 , doi : 10.1002 / anie.199616721 .
  5. ↑ Nicolaou, KC, Cole, Kevin P., Frederick, Michael O., Aversa, Robert J. and Denton, Ross M. (2007), Chemical Synthesis of the GHIJK Ring System and Further Experimental Support for the Originally Assigned Structure of Maitotoxin . Angew. Chem. Int. Ed., 46: 8875-8879. doi : 10.1002 / anie.200703742
  6. ↑ Chemical Synthesis of the GHIJKLMNO Ring System of Maitotoxin KC Nicolaou, Michael O. Frederick, Antonio CB Burtoloso, Ross M. Denton, Fatima Rivas, Kevin P. Cole, Robert J. Aversa, Romelo Gibe, Taiki Umezawa, and Takahiro Suzuki Journal of the American Chemical Society 2008 130 (23), 7466-7476 doi : 10.1021 / ja801139f
  7. ↑ Synthesis of the ABCDEFG Ring System of Maitotoxin KC Nicolaou, Robert J. Aversa, Jian Jin, and Fatima Rivas Journal of the American Chemical Society 2010 132 (19), 6855-6861 doi : 10.1021 / ja102260q
  8. ↑ Synthesis and Biological Evaluation of QRSTUVWXYZA ′ Domains of Maitotoxin KC Nicolaou, Philipp Heretsch, Tsuyoshi Nakamura, Anna Rudo, Michio Murata, and Keiichi Konoki Journal of the American Chemical Society Article 2014 ASAP doi : 10.1021 / ja509829e
  9. ↑ Chemistry's toughest total synthesis challenge put on hold by lack of funds . Katrina Kramer, January 15, 2015, Chemistry World.