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Cell-permeable beta-peptide inhibitors of p53/hDM2 complexation
Elizabeth A Harker1, Alanna Schepartz
1Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Abstract:
Look at what the cat(ionic motif) dragged in! We report a general strategy to increase the cell permeability of beta(3)-peptides. Introduction of a minimal cationic motif within the folded structure of a high-affinity beta(3)-peptide ligand for hDM2 led to molecules with high 3(14)-helical structure, high hDM2 affinity and sufficient cell permeability to upregulate p53-dependent genes in live mammalian cells. Minimally cationic beta(3)-peptides represent the critical first step towards a class of protease-resistant peptidomimetics that might modulate intracellular biological pathways.
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