273221-94-6Relevant articles and documents
Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates
Braun, Alexandra,Gallo, Francesca,Hambira, Chido M.,Hechler, Torsten,Kato, Brandon,Müller, Christoph,Matinkhoo, Kaveh,Pahl, Andreas,Perrin, David M.,Wei, Charlie,Wong, Antonio A. W. L.
, p. 10282 - 10292 (2021)
Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.