Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.
Basic Information
ID: ALA4376831
Journal: J Med Chem
Title: Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.
Authors: Dougherty PG, Wen J, Pan X, Koley A, Ren JG, Sahni A, Basu R, Salim H, Appiah Kubi G, Qian Z, Pei D.
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 β-catenin/TCF interactions resulted in the generation of potent proof-of-concept antiproliferative agents against key therapeutic targets.
CiteXplore: 31657556
DOI: 10.1021/acs.jmedchem.9b00456
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