Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates.
Chemistry
; 27(40): 10282-10292, 2021 Jul 16.
Article
em En
| MEDLINE
| ID: mdl-34058032
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoconjugados
/
Alfa-Amanitina
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article