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Cell‐Permeable β‐Peptide Inhibitors of p53/hDM2 Complexation
Author(s) -
Harker Elizabeth A.,
Schepartz Alanna
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900049
Subject(s) - peptidomimetic , peptide , intracellular , protease , chemistry , biochemistry , cell , biophysics , membrane permeability , cationic polymerization , cell permeability , microbiology and biotechnology , combinatorial chemistry , stereochemistry , membrane , biology , enzyme , organic chemistry
Look at what the cat(ionic motif) dragged in! We report a general strategy to increase the cell permeability of β 3 ‐peptides. Introduction of a minimal cationic motif within the folded structure of a high‐affinity β 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 β 3 ‐peptides represent the critical first step towards a class of protease‐resistant peptidomimetics that might modulate intracellular biological pathways.