Molecular Design of Cyclic Peptides with Cell Membrane Permeability and Development of MDMX-p53 Inhibitor.
ACS Med Chem Lett
; 14(9): 1174-1178, 2023 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-37736191
ABSTRACT
Cyclic peptides have been expected to be one of the modalities of intracellular protein-protein interaction (PPI) inhibitors, but they are generally known to have low cell membrane permeability. In this study, we focused on the conformation of cyclic peptides in the cell membrane to determine the requirement for their cell membrane permeability through passive diffusion. Utilizing the requirement, we searched for structures with high affinity for MDMX via computational chemistry and acquired cyclic peptide 19 (Papp = 0.80 × 10-6 cm s-1, IC50 = 0.07 µM).
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão