alpha-Amanitin: a possible suicide substrate-like toxin involving the sulphoxide moiety of the bridged cyclopeptide.
The highly hepatotoxic natural compound, alpha-amanitin, is noteworthy for its uncommon properties: high and specific affinity for the enzyme RNA polymerase type II, and, furthermore, high potency, severity and irreversibility of the poisoning. Considering the structural uniqueness of the tryptathionine bridge bearing a sulphoxide function, a few mechanistic and biochemical observations suggest that an enzyme-induced process may underlie the characteristics of the poisoning evolution which leads to the cytolysis of the hepatocytes.
Michelot
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D
Laboratoire de Chimie et de Biochimie, URA 401 CNRS, Muséum National d'Histoire Naturelle, Paris, France.
Labia
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R
D000546:Amanitins / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D010456:Peptides, Cyclic / Q000378:metabolism*; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D013454:Sulfoxides / Q000494:pharmacology*
D000546:Amanitins; D010456:Peptides, Cyclic; D013454:Sulfoxides; D012319:RNA Polymerase II