title: 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.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Harker
authors.forename: Alanna
authors.initials: A
authors.lastname: Schepartz
mesh_terms: D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D045325:HCT116 Cells; D006801:Humans; D018613:Microscopy, Confocal; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C433227:CNBP protein, human; D010455:Peptides; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53