A glycopolymer chaperone for fibroblast growth factor-2
A glycopolymer chaperone for fibroblast growth factor-2
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DOI：
10.1021/bc034138t
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发表时间：
2004-01-01
影响因子：
4.7
通讯作者：
Chaikof, EL
中科院分区：
文献类型：
--
作者：
Guan, R;Sun, XL;Chaikof, EL
以丙烯酰胺和丙烯酸酯衍生的单糖和二糖为原料，在氰脲酸酯的催化下，合成了含单糖和二糖的含糖共聚物。我们证明，糖基共聚物轴承悬垂，完全硫酸化乳糖单位有效地取代肝素和硫酸乙酰肝素作为成纤维细胞生长因子-2（FGF-2）的分子伴侣。具体地，鉴定了一种化合物，其保护FGF-2免受蛋白水解、酸和热诱导的降解，同时选择性地促进生长因子和受体二聚化。值得注意的是，这种肝素模拟物促进FGF-2特异性增殖细胞应答的能力得到了证实，并表明这种化合物和相关衍生物在与治疗性血管生成相关的领域中的潜在应用。
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.