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Cell-permeable beta-peptide inhibitors of p53/hDM2 complexation.

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.

SUBMITTER: Harker EA

PROVIDER: S-EPMC2995991 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Cell-permeable beta-peptide inhibitors of p53/hDM2 complexation.

Harker Elizabeth A EA Schepartz Alanna A

Chembiochem : a European journal of chemical biology 20090401 6

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 o ...[more]

PMID: 19266537

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