The occurrence of ansamers in the synthesis of cyclic peptides

• Published in: Nature communications Vol. 13; no. 1; pp. 6488 - 8
• Main Authors: Yao, Guiyang, Kosol, Simone, Wenz, Marius T., Irran, Elisabeth, Keller, Bettina G., Trapp, Oliver, Süssmuth, Roderich D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 140/131; 140/58; 639/638/403/935; 639/638/403/936; 639/638/92/349/977; 639/638/92/611; Alpha-Amanitin - chemistry; Amanitin; Amanitins - chemistry; Analogs; Crosslinking; Crystallography; Humanities and Social Sciences; Isomerism; Isomers; Molecular dynamics; multidisciplinary; Peptides; Peptides, Cyclic; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34125-8

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. The occurrence of isomers of the bicyclic octapeptide α-amanitin, which presents a macrolactam with a tryptathionine cross-link forming a handle, has been reported under the term of atropoisomers. Here, the authors synthesize its analogs and analyse their isomers, proposing and describing for them the term ansamer.