Document Detail


Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling.
MedLine Citation:
PMID:  22548447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  134     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-09     Completed Date:  2012-08-27     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7652-5     Citation Subset:  IM    
Affiliation:
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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