| Autor: |
Claudio Pisano, Concetta Aulicino, Loredana Vesci, Benito Casu, Annamaria Naggi, Giangiacomo Torri, Domenico Ribatti, Mirella Belleri, Marco Rusnati, Marco Presta |
| Předmět: |
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| Zdroj: |
Glycobiology; Feb2005, Vol. 15 Issue 2, p1-6C, 6p |
| Abstrakt: |
Vascular endothelial growth factor (VEGF) represents a target for antiangiogenic therapies in a wide spectrum of diseases, including cancer. As a novel strategy to generate nonanticoagulant antiangiogenic substances exploiting binding to VEGF while preventing receptor engagement, we assessed the VEGF-antagonist activity of a low-molecular-weight (LMW) compound (ST2184, Mw = 5800) generated by depolymerization of an undersulfated glycol-split heparin derivative. The parental compound was obtained by introducing regular sulfation gaps along the prevalently N-sulfated heparin regions, followed by glycol-splitting of all nonsulfated uronic acid residues (~50% of total uronic acid residues). ST2184 was endowed with a negligible anticoagulant activity after S.C. injection in mice. ST2184 binds VEGF165 as evaluated by its capacity to retard 125I-VEGF165 electrophoretic migration in a gel mobility shift assay and to prevent VEGF165 interaction with heparin immobilized onto a BIAcore sensor chip. Unlike heparin, ST2184 was unable to present 125I-VEGF165 to its high-affinity receptors in endothelial cells and inhibited VEGF165-induced neovascularization in the chick embryo chorioallantoic membrane. Undersulfated, LMW glycol-split heparins may therefore provide the basis for the design of novel nonanticoagulant angiostatic compounds. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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