A glycopolymer chaperone for fibroblast growth factor-2.
Mono- and disaccharide-containing glycopolymers were synthesized by cyanoxyl-mediated polymerization of acrylamide with acrylate-derivatized mono- and disaccharides. We demonstrate that a glycopolymer bearing pendant, fully sulfated lactose units effectively replaces heparin and heparan sulfate as a molecular chaperone for fibroblast growth factor-2 (FGF-2). Specifically, a compound was identified that protects FGF-2 from proteolytic, acid, and heat-induced degradation, while selectively promoting growth factor and receptor dimerization. Significantly, the capacity of this heparin-mimic to promote an FGF-2 specific proliferative cell response was confirmed and suggests potential applications for this compound and related derivatives in areas related to therapeutic angiogenesis.
Guan
Ran
R
Departments of Surgery and Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia 30322.
Sun
Xue-Long
XL
Hou
Sijian
S
Wu
Peiyi
P
Chaikof
Elliot L
EL
D000143:Acids; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006358:Hot Temperature; D006868:Hydrolysis; D007202:Indicators and Reagents; D051379:Mice; D018832:Molecular Chaperones / Q000138:chemical synthesis* / Q000737:chemistry; D018716:Molecular Mimicry; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism; D012997:Solvents; D014357:Trypsin
D000143:Acids; D007202:Indicators and Reagents; D018832:Molecular Chaperones; D011108:Polymers; D017468:Receptors, Fibroblast Growth Factor; D012997:Solvents; D016222:Fibroblast Growth Factor 2; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D014357:Trypsin