The occurrence of ansamers in the synthesis of cyclic peptides.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
30 10 2022
Historique:
received: 20 05 2022
accepted: 14 10 2022
entrez: 31 10 2022
pubmed: 1 11 2022
medline: 2 11 2022
Statut: epublish

Résumé

α-Amanitin is a bicyclic octapeptide composed of a macrolactam with a tryptathionine cross-link forming a handle. Previously, the occurrence of isomers of amanitin, termed atropisomers has been postulated. Although the total synthesis of α-amanitin has been accomplished this aspect still remains unsolved. We perform the synthesis of amanitin analogs, accompanied by in-depth spectroscopic, crystallographic and molecular dynamics studies. The data unambiguously confirms the synthesis of two amatoxin-type isomers, for which we propose the term ansamers. The natural structure of the P-ansamer can be ansa-selectively synthesized using an optimized synthetic strategy. We believe that the here described terminology does also have implications for many other peptide structures, e.g. norbornapeptides, lasso peptides, tryptorubins and others, and helps to unambiguously describe conformational isomerism of cyclic peptides.

Identifiants

pubmed: 36310176
doi: 10.1038/s41467-022-34125-8
pii: 10.1038/s41467-022-34125-8
pmc: PMC9618573
doi:

Substances chimiques

Alpha-Amanitin 0
Peptides, Cyclic 0
Amanitins 0
Peptides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6488

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Guiyang Yao (G)

Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany.
Center for Innovative Drug Discovery, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, Shanghai, PR China.

Simone Kosol (S)

Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany.

Marius T Wenz (MT)

Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany.

Elisabeth Irran (E)

Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany.

Bettina G Keller (BG)

Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany.

Oliver Trapp (O)

Department of Chemistry and Pharmacy, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377, Munich, Germany.
Max-Planck-Institute for Astronomy, Königstuhl 17, 69117, Heidelberg, Germany.

Roderich D Süssmuth (RD)

Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany. suessmuth@chem.tu-berlin.de.

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Classifications MeSH