Anginex, a designed peptide that inhibits angiogenesis

A. W. Griffioen, D. W.J. Van der Schaft, A. F. Barendsz-Janson, A. Cox, H. A.J. Struijker Boudier, H. F.P. Hillen, K. H. Mayo

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

Novel β-sheet-forming peptide 33-mers, βpep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences from the β-sheet domains of anti-angiogenic proteins. One of these designed peptides (βpep-25), named anginex, was observed to be potently anti-angiogenic. Anginex specifically inhibits vascular endothelial cell proliferation and induces apoptosis in these cells, as shown by flow-cytometric detection of sub-diploid cells, TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-nick-end labelling) analysis and cell morphology. Anginex also inhibits endothelial cell adhesion to and migration on different extracellular matrix components. Inhibition of angiogenesis in vitro is demonstrated in the sprout-formation assay and in vivo in the chick embryo chorio-allantoic membrane angiogenesis assay. Comparison of active and inactive βpep sequences allows structure-function relationships to be deduced. Five hydrophobic residues and two lysines appear to be crucial to activity. This is the first report of a designed peptide having a well-defined biological function as a novel cytokine, which may be an effective anti-angiogenic agent for therapeutic use against various pathological disorders, such as neoplasia, rheumatoid arthritis, diabetic retinopathy and restenosis.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalBiochemical Journal
Volume354
Issue number2
DOIs
StatePublished - Mar 1 2001

Keywords

  • Apoptosis
  • Cytokine
  • Design
  • Endothelium
  • Structure

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