Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility

Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-term...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Organic letters 2023-06, Vol.25 (24), p.4489-4492
Hauptverfasser: Reja, Rahi M., Chau, Brittney, Gao, Jianmin
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-terminus Cys-Cys cross-linking. The bicyclization is fast, affords quantitative conversion, and tolerates various side chain functionalities. Importantly, the resulting diazaborine linkage, while stable at a neutral pH, can readily reverse upon mild acidification to give pH-responsive peptides.
ISSN:1523-7060
1523-7052
1523-7052
DOI:10.1021/acs.orglett.3c01496