Wang H, Toida T, Kim Y S, Capila I, Hileman R E, Bernfield M, Linhardt R J
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biochem Biophys Res Commun. 1997 Jun 18;235(2):369-73. doi: 10.1006/bbrc.1997.6789.
Fibroblast growth factors are important heparin binding, mitogenic proteins. The binding site in heparin and heparan sulfate for fibroblast growth factor-2 (basic fibroblast growth factor) has been described as rich in glucosamine-2-sulfate 1-->4 linked to iduronic acid-2-sulfate. The glucosamine residue in the heparin binding site is also 6-sulfated. A new glycosaminoglycan, acharan sulfate, has been chemically modified to prepare a polysaccharide, N-sulfoacharan sulfate, consisting of glucosamine-2-sulfate 1-->4 linked to iduronic acid-2-sulfate. Acharan sulfate binds very weakly to fibroblast growth factor-2 while N-sulfoacharan sulfate binds with nearly the same affinity as heparin. Mitogenicity studies were performed using heparan sulfate-free cells stably transfected with fibroblast growth factor receptor-1. Acharan sulfate inhibits heparin's enhancement of fibroblast growth factor-2 mitogenic activity, without affecting cell viability, while N-sulfoacharan sulfate shows heparin-like activity but at a greatly reduced level. These results suggest additional mechanisms not requiring high affinity glycosaminoglycan binding to fibroblast growth factor-2 may be important in its mitogenic activity.
成纤维细胞生长因子是重要的肝素结合促有丝分裂蛋白。肝素和硫酸乙酰肝素中成纤维细胞生长因子-2（碱性成纤维细胞生长因子）的结合位点已被描述为富含与艾杜糖醛酸-2-硫酸酯以1→4相连的氨基葡萄糖-2-硫酸酯。肝素结合位点中的氨基葡萄糖残基也是6-硫酸化的。一种新的糖胺聚糖，硫酸乙酰肝素，已被化学修饰以制备一种多糖，N-磺基硫酸乙酰肝素，其由与艾杜糖醛酸-2-硫酸酯以1→4相连的氨基葡萄糖-2-硫酸酯组成。硫酸乙酰肝素与成纤维细胞生长因子-2的结合非常弱，而N-磺基硫酸乙酰肝素的结合亲和力与肝素几乎相同。使用稳定转染有成纤维细胞生长因子受体-1的无硫酸乙酰肝素细胞进行了促有丝分裂活性研究。硫酸乙酰肝素抑制肝素对成纤维细胞生长因子-2促有丝分裂活性的增强作用，而不影响细胞活力，而N-磺基硫酸乙酰肝素显示出肝素样活性，但水平大大降低。这些结果表明，在其促有丝分裂活性中，可能存在不需要与成纤维细胞生长因子-2进行高亲和力糖胺聚糖结合的其他机制。
