Struktur und Wirkung der Amatoxine

TLDR: Bisnor-deoxy-amanineamide, a synthetic compound having the features of the highly toxic natural products in simplified form, inhibits RNA synthesis by 90% at a concentration of 40 ~tg/ml.

Abstract: The amatoxins, mainly 0cand fl-amanitine, are the essential lethal poisons of the toadstool Amanita phalloides. Structurally they are cyclic octapeptides whose ring is divided and held in compact shape by a sulfoxide bridge. Chemical changes in the molecule, like scission of one of the rings or alterations at the y=hydroxylated isoleucine side chain, may reduce or even eliminate toxicity. The toxic action can be attributed to a biological property of the toxins operating at molecular level: extremely strong inhibition of one of the eucaryotic RNA polymerases (form II resp. B). Bisnor-deoxy-amanineamide, a synthetic compound having the features of the highly toxic natural products in simplified form, inhibits RNA synthesis by 90% at a concentration of 40 ~tg/ml. I t is t03 times less active than the natural amatoxins and therefore nontoxic.