Abstract
The binding interactions of the phosphosulfomannan anticancer agent PI-88 (1) with the angiogenic growth factors FGF-1, FGF-2, and VEGF were studied by surface plasmon resonance (SPR) on a BIAcore 3000 biosensor. Compared with heparin, PI-88 has at least 11-fold higher affinity for FGF-1 and at least 3-fold higher affinity for VEGF, but at least 13-fold lower affinity for FGF-2. To define the structural features of PI-88 that are important for growth factor binding, several analogues, such as dephosphorylated PI-88 and a sulfated pentasaccharide, were prepared. The binding interactions of these analogues with FGF-1, FGF-2, and VEGF were similarly studied by SPR, and structure-activity relationships were determined.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inducing Agents / chemistry*
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Biosensing Techniques
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Chemical Phenomena
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Chemistry, Physical
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Endothelial Growth Factors / chemistry
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Fibroblast Growth Factor 1 / chemistry
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Fibroblast Growth Factor 2 / chemistry
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Heparin / chemistry
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Intercellular Signaling Peptides and Proteins / chemistry
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Kinetics
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Lymphokines / chemistry
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Mannans / chemistry*
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Oligosaccharides / chemistry*
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Oligosaccharides / isolation & purification
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Pichia / chemistry
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Sulfates / chemistry
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Surface Plasmon Resonance
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Angiogenesis Inducing Agents
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Mannans
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Oligosaccharides
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Sulfates
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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phosphomannopentaose sulfate
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Fibroblast Growth Factor 2
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Fibroblast Growth Factor 1
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Heparin