MYC-Targeting Inhibitors Generated from a Stereodiversified Bicyclic Peptide Library.
J Am Chem Soc
; 146(2): 1356-1363, 2024 01 17.
Article
em En
| MEDLINE
| ID: mdl-38170904
ABSTRACT
Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biblioteca de Peptídeos
/
Espectrometria de Massas em Tandem
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article