TY - JOUR
T1 - Anginex, a designed peptide that inhibits angiogenesis
AU - Griffioen, A.W.
AU - Schaft, van der, D.W.J.
AU - Barendsz-Janson, A.F.
AU - Cox, A.
AU - Struijker Boudier, H.A.J.
AU - Hillen, H.F.P.
AU - Mayo, K.H.
PY - 2001
Y1 - 2001
N2 - Novel b-sheet-forming peptide 33-mers, bpep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences from the b-sheet domains of anti-angiogenic proteins. One of these designed peptides (bpep-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 bpep 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.
AB - Novel b-sheet-forming peptide 33-mers, bpep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences from the b-sheet domains of anti-angiogenic proteins. One of these designed peptides (bpep-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 bpep 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.
U2 - 10.1042/0264-6021:3540233
DO - 10.1042/0264-6021:3540233
M3 - Article
SN - 0264-6021
VL - 354
SP - 233
EP - 242
JO - Biochemical Journal
JF - Biochemical Journal
IS - 2
ER -
