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.
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March 2001
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Research Article|
February 22 2001
Anginex, a designed peptide that inhibits angiogenesis
Arjan W. GRIFFIOEN;
Arjan W. GRIFFIOEN
*Tumor Angiogenesis Laboratory, Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands,
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Daisy W. J. VAN DER SCHAFT;
Daisy W. J. VAN DER SCHAFT
*Tumor Angiogenesis Laboratory, Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands,
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Annemarie F. BARENDSZ-JANSON;
Annemarie F. BARENDSZ-JANSON
*Tumor Angiogenesis Laboratory, Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands,
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Andrew COX;
Andrew COX
†Department of Biochemistry, 6-155 Jackson Hall, University of Minnesota, Health Sciences Center, 321 Church Street, Minneapolis, MN 55455, U.S.A.
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Harry A. J. STRUIJKER BOUDIER;
Harry A. J. STRUIJKER BOUDIER
‡Department of Pharmacology, Maastricht University, Universiteitssingel 50, 6202 AZ Maastricht, The Netherlands
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Harry F. P. HILLEN;
Harry F. P. HILLEN
*Tumor Angiogenesis Laboratory, Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands,
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Kevin H. MAYO
Kevin H. MAYO
1
†Department of Biochemistry, 6-155 Jackson Hall, University of Minnesota, Health Sciences Center, 321 Church Street, Minneapolis, MN 55455, U.S.A.
1To whom correspondence should be addressed (e-mail mayox001@tc.umn.edu).
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Publisher: Portland Press Ltd
Received:
September 11 2000
Revision Received:
November 08 2000
Accepted:
December 08 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 354 (2): 233–242.
Article history
Received:
September 11 2000
Revision Received:
November 08 2000
Accepted:
December 08 2000
Citation
Arjan W. GRIFFIOEN, Daisy W. J. VAN DER SCHAFT, Annemarie F. BARENDSZ-JANSON, Andrew COX, Harry A. J. STRUIJKER BOUDIER, Harry F. P. HILLEN, Kevin H. MAYO; Anginex, a designed peptide that inhibits angiogenesis. Biochem J 1 March 2001; 354 (2): 233–242. doi: https://doi.org/10.1042/bj3540233
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