α-amanitin
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| Surname | α-amanitin | |||||||||||||||
| Molecular formula | C 39 H 54 N 10 O 14 S. | |||||||||||||||
| Brief description |
colorless to yellowish solid |
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| properties | ||||||||||||||||
| Molar mass | 919.09 g mol −1 | |||||||||||||||
| Physical state |
firmly |
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| Melting point |
254-255 ° C |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
α-Amanitin is one of the amatoxins and, like all these, is a bicyclic peptide made up of eight amino acids .
It differs in its structure only through the amide nitrogen in the asparagine residue from β-amanitin, from γ-amanitin only through a hydroxyl group in the dihydroxy isoleucine residue . These, too, are water-soluble, heat-resistant compounds that are not destroyed in the gastrointestinal tract of humans and block the formation of new proteins in cells with about the same effectiveness .
This means that α-, β- and γ-amanitin and other amatoxins are among the most dangerous active ingredients that occur naturally. They are available in various types of fungi contain, especially in the countryside amanita ( Amanita phalloides ). Even small amounts lead to severe poisoning, an amatoxin syndrome .
Occurrence
Α-Amanitin is found in different types of mushrooms. In Central Europe, this includes in the genus Amanita ( Amanita ) some species of Amanita mushrooms , namely Amanita phalloides ( A. phalloides ), Amanita virosa ( A. virosa ) and Spring Knollenblätterpilz ( A. verna ). In addition, species of the genus umbrella flies ( Lepiota ) also contain the compound, likewise the poison hood ( Galerina marginata ) as well as representatives of the genus velvet cap ( Conocybe ).
The α-Amanitin can be detected qualitatively and quantitatively in physiological test material by ELISA tests and highly specifically by coupling HPLC with mass spectrometry after appropriate sample preparation .
biosynthesis
In contrast to many other cyclic peptides in fungi, amatoxins and phallotoxins are not synthesized non-ribosomally , but rather as part of ribosomal protein synthesis . The mRNA of the AMA1 gene necessary for such a biosynthesis of α-Amanitin in Amanita phalloides codes for a proprotein of 36 amino acids, in Amanita bisporigera of 35 AA. The octapeptide is cut out of this and cyclized. Since the eight central amino acids are flanked by prolins , it is assumed that prolyl oligopeptidases process the protein.
properties
α-Amanitin is a flammable, but difficult to ignite, colorless to yellowish solid that is sparingly soluble in water. The bicyclic octapeptide is not destroyed by cooking and also not broken down by proteases in the digestive tract.
Toxicity
In human and generally in eukaryotic cells, it inhibits the DNA-dependent RNA polymerase II , which is required for the synthesis of mRNA. This leads to the interruption of protein synthesis and cell death .
use
α-Amanitin is used for the scientific investigation of RNA polymerase II. α-Amanitin is the active ingredient in several antibody-drug conjugates (ADC) under development .
Individual evidence
- ↑ a b c d e f g Entry on alpha-Amanitin in the GESTIS substance database of the IFA , accessed on January 10, 2017(JavaScript required) .
- ^ ADC Review: α-Amanitin , accessed July 12, 2016.
- ↑ Data sheet α-Amanitin, from at Sigma-Aldrich , accessed on July 12, 2016 ( PDF ).
- ^ Albert Gossauer: Structure and reactivity of biomolecules , Verlag Helvetica Chimica Acta, Zurich, 2006, p. 441, ISBN 978-3-906390-29-1 .
- ↑ Hans W. Kothe, Erika Kothe: mushrooms an entertaining introduction to mycology . LIT Verlag Münster, 2010, ISBN 978-3-643-10914-9 , pp. 27 ( limited preview in Google Book search).
- ↑ H. Luo, H. Hallen-Adams, J. Scott-Craig, J. Walton: Ribosomal biosynthesis of α-amanitin in Galerina marginata. PMID 22202811 , DOI: 10.1016 / j.fgb.2011.12.005 , PMC 3997167 (free full text)
- ↑ awl.ch: Determination of α-Amanitin in fungi and clinical samples (blood, urine) with LC-MS , accessed on July 12, 2016.
- ↑ See UniProt entry Amatoxin .
- ^ HE Hallen, H. Luo, JS Scott-Craig, JD Walton: Gene family encoding the major toxins of lethal Amanita mushrooms. In: Proceedings of the National Academy of Sciences . Volume 104, number 48, November 2007, pp. 19097-19101, doi : 10.1073 / pnas.0707340104 , PMID 18025465 , PMC 2141914 (free full text).
- ↑ Jonathan D. Walton, Heather E. Hallen-Adams, Hong Luo: Ribosomal Biosynthesis of the Cyclic Peptide Toxins of Amanita Mushrooms. In: Biopolymers. Volume 94, No. 5, 2010, p. 659, doi: 10.1002 / bip.21416, PMID 20564017 , PMC 4001729 (free full text).
- ↑ F. Brueckner, P. Cramer: Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation. In: Nature Structural & Molecular Biology. Volume 15, August 2008, pp. 811-818, PMID 18552824 .
- ↑ a b aerzteblatt.de: Deutsches Ärzteblatt: Plant substances for tumor treatment: Amanitin as a cancer therapeutic , accessed on July 12, 2016.
- ↑ B. Meinecke, S. Meinecke-Tillmann: Effects of α-amanitin on nuclear maturation of porcine oocytes in vitro. In: Reproduction. 98, 1993, p. 195, doi: 10.1530 / jrf.0.0980195 .
- ↑ Stephen Parmley: Resurrecting a Magic Bullet. In: Science-Business eXchange. 7, 2014, doi : 10.1038 / scibx.2014.1397 .
- ↑ K. Van der Jeught, HC Xu, YJ Li, XB Lu, G. Ji: Drug resistance and new therapies in colorectal cancer. In: World Journal of Gastroenterology . Volume 24, number 34, September 2018, pp. 3834-3848, doi : 10.3748 / wjg.v24.i34.3834 , PMID 30228778 , PMC 6141340 (free full text) (review).