Abstract
Based on structure-activity relationships of the angiostatic beta-sheet-forming peptide anginex, we have designed a mimetic, 6DBF7, which inhibits angiogenesis and tumor growth in mice. 6DBF7 is composed of a beta-sheet-inducing dibenzofuran (DBF)-turn mimetic and two short key amino acid sequences from anginex. This novel antiangiogenic molecule is more effective in vivo than parent anginex. In a mouse xenograft model for ovarian carcinoma, 6DBF7 is observed to reduce tumor growth by up to 80%. It is suggested that the activity is based on antiangiogenesis, because in vitro tube formation is inhibited, and because treatment of tumor-bearing mice led to a significant reduction in microvessel density within the tumor. This partial peptide mimetic is the first endothelial cell-specific molecule designed as a substitute for an angiostatic inhibitory peptide.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / chemistry
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Amino Acid Sequence
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Antineoplastic Agents / pharmacology*
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Benzofurans / chemistry
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Cell Division
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Cell Line, Tumor
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Cells, Cultured
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Endothelium, Vascular / metabolism
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Female
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Humans
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Immunohistochemistry
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In Situ Nick-End Labeling
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Nude
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Models, Molecular
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Molecular Sequence Data
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Neoplasm Transplantation
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Ovarian Neoplasms
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Peptides / chemistry*
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Protein Structure, Secondary
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Proteins / chemistry*
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Proteins / pharmacology*
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
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Time Factors
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Umbilical Veins / cytology
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Benzofurans
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Peptides
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Proteins
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betapep-25 protein, synthetic
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dibenzofuran
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Alanine