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Abstract

α-AMANITIN, a cyclic peptide of the toadstool Amanita phalloides1,2, causes necrosis of liver and kidney cells, the first morphological lesions occurring in the nuclei3,4. It acts by binding to RNA polymerase in eukaryotic .cells and inhibiting the enzyme5–9. The hepatotoxicity of amanitin increases several times when it is conjugated to albumin, probably because of a slower rate of elimination of the toxin through the glomeruli4,10. It is unlikely that the amanitin-albumin conjugate enters the hepatocyte by a mechanism involving its albumin moiety; it was therefore suggested11 that penetration of the liver cells is consequent on binding of the amanitin group to the carrier involved in transport of this peptide. This led us to consider more generally the facilitation of penetration into cells by large molecules by means of binding to another molecule for which a carrier exists on the cell membrane12,13.