Design, synthesis, and biochemical evaluation of alpha-amanitin derivatives containing analogs of the trans-hydroxyproline residue for potential use in antibody-drug conjugates.
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.
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
74
References
1
Citations
NaN
KQI