Design of a Partial Peptide Mimetic of Anginex with Antiangiogenic and Anticancer Activity

Kevin H. Mayo, Ruud P.M. Dings, Carolee Flader, Irina Nesmelova, Balasz Hargittai, Daisy W.J. Van Der Schaft, Loes I. Van Eijk, Dinesha Walek, Judy Haseman, Thomas R. Hoye, Arjan W. Griffioen

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Based on structure-activity relationships of the angiostatic β-sheet-forming peptide anginex, we have designed a mimetic, 6DBF7, which inhibits angiogenesis and tumor growth in mice. 6DBF7 is composed of a β-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.

Original languageEnglish (US)
Pages (from-to)45746-45752
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
StatePublished - Nov 14 2003

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    Mayo, K. H., Dings, R. P. M., Flader, C., Nesmelova, I., Hargittai, B., Van Der Schaft, D. W. J., Van Eijk, L. I., Walek, D., Haseman, J., Hoye, T. R., & Griffioen, A. W. (2003). Design of a Partial Peptide Mimetic of Anginex with Antiangiogenic and Anticancer Activity. Journal of Biological Chemistry, 278(46), 45746-45752. https://doi.org/10.1074/jbc.M308608200