Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.
J Med Chem
; 62(22): 10098-10107, 2019 11 27.
Article
em En
| MEDLINE
| ID: mdl-31657556
ABSTRACT
Stapled peptides recapitulate the binding affinity and specificity of α-helices in proteins, resist proteolytic degradation, and may provide a novel modality against challenging drug targets such as protein-protein interactions. However, most of the stapled peptides have limited cell permeability or are impermeable to the cell membrane. We show herein that stapled peptides can be rendered highly cell-permeable by conjugating a cyclic cell-penetrating peptide to their N-terminus, C-terminus, or stapling unit. Application of this strategy to two previously reported membrane-impermeable peptidyl inhibitors against the MDM2/p53 and ß-catenin/TCF interactions resulted in the generation of potent proof-of-concept antiproliferative agents against key therapeutic targets.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteína Supressora de Tumor p53
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Proteínas Proto-Oncogênicas c-mdm2
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Beta Catenina
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article