Probing the interactions of phosphosulfomannans with angiogenic growth factors by surface plasmon resonance.
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.
Cochran
Siska
S
Drug Design Group, Progen Industries Limited, Brisbane, Richlands BC, Queensland 4077, Australia.
Li
Caiping
C
Fairweather
Jon K
JK
Kett
Warren C
WC
Coombe
Deirdre R
DR
Ferro
Vito
V
D043925:Angiogenesis Inducing Agents / Q000737:chemistry*; D015374:Biosensing Techniques; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016228:Endothelial Growth Factors / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D007700:Kinetics; D008222:Lymphokines / Q000737:chemistry; D008351:Mannans / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification; D010843:Pichia / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013431:Sulfates / Q000737:chemistry; D020349:Surface Plasmon Resonance; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008351:Mannans; D009844:Oligosaccharides; D013431:Sulfates; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C120158:phosphomannopentaose sulfate; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin