| Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling. | |
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MedLine Citation:
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PMID: 22548447 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diverse strategies have been explored to mimic the surface displayed by an α-helical segment of a protein, with the goal of creating inhibitors of helix-mediated protein-protein interactions. Many recognition surfaces on proteins, however, are topologically more complex and less regular than a single α-helix. We describe efforts to develop peptidic foldamers that bind to the irregular receptor-recognition surface of vascular endothelial growth factor (VEGF). Our approach begins with a 19-residue α-peptide previously reported by Fairbrother et al. (Biochemistry 1998, 37, 17754) to bind to this surface on VEGF. Systematic evaluation of α→β replacements throughout this 19-mer sequence enabled us to identify homologues that contain up to ~30% β residues, retain significant affinity for VEGF, and display substantial resistance to proteolysis. These α/β-peptides can block VEGF-stimulated proliferation of human umbilical vein endothelial cells. |
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Authors:
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Holly S Haase; Kimberly J Peterson-Kaufman; Sheeny K Lan Levengood; James W Checco; William L Murphy; Samuel H Gellman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-05-01 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 134 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-09 Completed Date: 2012-08-27 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 7652-5 Citation Subset: IM |
Affiliation:
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Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Cell Proliferation / drug effects Human Umbilical Vein Endothelial Cells Humans Models, Molecular Molecular Sequence Data Peptides / chemistry*, pharmacology* Protein Folding Protein Structure, Secondary Signal Transduction / drug effects* Vascular Endothelial Growth Factor A / antagonists & inhibitors*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GM056414/GM/NIGMS NIH HHS; HL093282/HL/NHLBI NIH HHS; R01 GM056414/GM/NIGMS NIH HHS; R01 HL093282/HL/NHLBI NIH HHS; T32 GM008349/GM/NIGMS NIH HHS; T32 GM008349/GM/NIGMS NIH HHS; T32 GM008505/GM/NIGMS NIH HHS; T32 GM008505/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Peptides; 0/Vascular Endothelial Growth Factor A |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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