Iodine-Mediated Tryptathionine Formation Facilitates the Synthesis of Amanitins.
J Am Chem Soc
; 143(35): 14322-14331, 2021 09 08.
Article
en En
| MEDLINE
| ID: mdl-34459587
ABSTRACT
Synthetic methods on the macrocyclization of peptides are of high interest since they facilitate the synthesis of various types of potentially bioactive compounds, e.g. addressing targets like protein-protein-interactions. Herein, we report on an efficient method to construct tryptathionine-cross-links in peptides between the amino acids Trp and Cys. This reaction not only is the basis for the total synthesis of the death cap toxin α-amanitin but also provides rapid access to various new amanitin analogues. This study for the first time presents a systematic compilation of structure-activity relations (SAR) of amatoxins with regard to RNA polymerase II inhibition and cytotoxicity with one amanitin derivative of superior RNAP II inhibition. The present approach paves the way for the synthesis of structurally diverse amatoxins as future payloads for antibody-toxin conjugates in cancer therapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Am Chem Soc
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania