A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors.
Angew Chem Int Ed Engl
; 62(7): e202214815, 2023 02 06.
Article
em En
| MEDLINE
| ID: mdl-36535892
Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5-6Q, that targets human histone deacetylase 8 (HDAC8) with a KD value of 15â
nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Peptídeos Cíclicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2023
Tipo de documento:
Article