Solution Structure of a β-Peptide Ligand for hDM2
نویسندگان
چکیده
منابع مشابه
Solution structure of a beta-peptide ligand for hDM2.
We recently reported a beta-peptide foldamer, beta53-1, that folds into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and potently inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). Here, we present the solution structure of beta53-1 in methanol. Details of the structure illustrate fundamental and novel el...
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Regulation of the transcriptional response to the tumor suppressor p53 occurs at many levels, including control of its transcriptional activity, and of its stability and concentration within the cell. p53 stability is regulated by the protein Hdm2, an E3 ubiquitin ligase that binds to p53 and promotes its ubiquitination and degradation. The C-terminal domain of Hdm2, which is critical for this ...
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Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-parallel beta-sheet comprising residues 15-18 and 37-40 and a small 3(10) helix spanning residues 10-12. The ov...
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hDM2 is recognized in vivo by a short alpha-helix within the p53 trans-activation domain (p53AD). Disruption of the p53.hDM2 interaction is an important goal for cancer therapy. A functional epitope comprised of three residues on one face of the p53AD helix (F19, W23, and L26) contributes heavily to the binding free energy. We hypothesized that the p53AD functional epitope would be recapitulate...
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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 m...
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ژورنال
عنوان ژورنال: Journal of the American Chemical Society
سال: 2005
ISSN: 0002-7863,1520-5126
DOI: 10.1021/ja042933r