Cell-permeable beta-peptide inhibitors of p53/hDM2 complexation.
نویسندگان
چکیده
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.
منابع مشابه
Bridged beta(3)-peptide inhibitors of p53-hDM2 complexation: correlation between affinity and cell permeability.
Beta-peptides possess several features that are desirable in peptidomimetics; they are easily synthesized, fold into stable secondary structures in physiologic buffers, and resist proteolysis. They can also bind to a diverse array of proteins to inhibit their interactions with alpha-helical ligands. beta-peptides are usually not cell-permeable, however, and this feature limits their utility as ...
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متن کاملHelical beta-peptide inhibitors of the p53-hDM2 interaction.
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The design of novel protein ligands and inhibitors of protein– protein interactions is an important goal in post-genomic proteome analyses and in drug and vaccine discovery. Unfortunately, the design of synthetic molecules that target surface-exposed regions on folded proteins is presently difficult. Moreover, typical libraries of small “druglike” compounds have so far not been a fruitful sourc...
متن کاملThermodynamic and computational studies on the binding of p53-derived peptides and peptidomimetic inhibitors to HDM2.
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عنوان ژورنال:
- Chembiochem : a European journal of chemical biology
دوره 10 6 شماره
صفحات -
تاریخ انتشار 2009