肝素酶在医药领域应用的研究进展

Research progress of heparinase in the field of medicine

摘要:

肝素酶是一类能够特定切割肝素或硫酸乙酰肝素中α-1,4糖苷键并将其裂解成有活性寡糖片段的酶，主要分为真核生物肝素酶 (Heparanase) 和原核生物肝素酶 (Heparinase)。由于原核生物肝素酶是一种高效绿色的生物催化剂，因此近年来在医药领域的应用性研究逐渐被重视。文中结合本课题组相关工作，归纳介绍了原核生物肝素酶通过作用于硫酸肝素蛋白聚糖 (HSPGs)生成肝素小分子，抑制肿瘤细胞增殖方面的应用；原核生物肝素酶在制备第三代创新型抗凝血药物低分子量肝素 (Low molecular weight heparin, LWMH) 和超低分子量肝素 (Ultra low molecular weight heparin, ULMWH) 方面的应用；原核生物肝素酶作为肝素拮抗药物等医药领域的重要应用；并展望了原核生物肝素酶的未来应用前景及挑战。

Abstract:

Heparinases can produce biologically active oligosaccharides by specifically cleaving the α-(1,4) glycosidic linkages of heparin and heparan sulphate. Heparinases are divided into heparinase and heparanase. Because heparinase is an effective biocatalyst, more and more researchers pay attention to the application of heparinase in medical field in the recent years. Combined with the related research work in our group, the application value of heparinase in the medical field was summarized, such as the determination of the structure of heparin, the preparation of low-molecular-weight heparin and ultra-low-molecular-weight heparin, tumor therapy and as a heparin antagonist. In addition, we summarized the definition, source of heparinase and its application in the medicine field. Heparinases have a great application prospect in the field of medicine.