The Effect of the Chemical Nature of the Side Chains of the Amatoxins in the Inhibition of Eukaryotic RNA Polymerase B
- 1 June 1981
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 117 (1) , 161-164
- https://doi.org/10.1111/j.1432-1033.1981.tb06315.x
Abstract
The inhibition constants (Ki) of DNA-dependent RNA polymerase B (or II) from calf thymus were measured for eight synthetically obtained bicyclic amanitin-like thioethers, two R-sulfoxides, and two S-sulfoxides. These Ki values were compared with those of alpha-amanitin, its 6'-O-methylether Ia (an R-sulfoxide), the S-sulfoxide, the sulfone, the S-deoxo derivative (Id) of Ia, and several previously described amatoxins. The necessity of a beta-methyl side chain in position 3 and a hydroxy group in proline-2 was confirmed. Additionally, the presence of an isoleucine side chain in position 6 and the absence of a side chain in position 5 was recognized as important for binding to the enzyme. In the three sulfoxide samples examined, the R-diastereomer was found to be a stronger inhibitor than the S-form. The contribution of every structural element to biological activity has been discussed.Keywords
This publication has 11 references indexed in Scilit:
- The effects of several divalent cations on the activation or inhibition of RNA polymerases IIArchives of Biochemistry and Biophysics, 1980
- Amaninamide, a new toxin ofAmanita virosa mushroomsCellular and Molecular Life Sciences, 1980
- Conformation of the mushroom toxin β-amanitin in the crystalline stateBiochemistry, 1978
- Amatoxins, Phallotoxins, Phallolysin, and Antamanide: The Biologically Active Components of PoisonousAmanitaMushroomCRC Critical Reviews in Biochemistry, 1978
- Selective reduction of sulfoxidesThe Journal of Organic Chemistry, 1977
- Identification of the amatoxin-binding subunit of RNA polymerase B by affinity labeling experiments. Subunit B 3 - the true amatoxin receptor protein of multiple RNA polymerase BBiochemistry, 1976
- Über die Inhaltsstoffe des grünen Knollenblätterpilzes, XLVII1) Proamanullin und Amanullinsäure sowie zwei unbekannte Derivate des β‐Amanitins; die restlichen Mitglieder der AmanitinfamilieEuropean Journal of Organic Chemistry, 1974
- Über die Inhaltsstoffe des grünen Knollenblätterpilzes, XL. Oxydation und Reduktion an der γ.δ‐Dihydroxy‐isoleucin‐Seitenkette des O‐Methyl‐α‐amanitins. Methyl‐aldoamanitin, ein ungiftiges AbbauproduktEuropean Journal of Organic Chemistry, 1970
- über die Giftstoffe des grünen Knollenblätterpilzes, XIX. Umwandlung von β‐Amanitin in α‐AmanitinEuropean Journal of Organic Chemistry, 1960
- Über die Giftstoffe des Knollenblätterpilzes. VI. Amanitin, das Hauptgift des KnollenblätterpilzesEuropean Journal of Organic Chemistry, 1941