天然多糖作为蛋白质药物化学修饰剂的研究进展

Advances in the research of natural polysaccharides for modification of protein drugs

蛋白质工程和基因工程技术的迅速发展迎来了蛋白质类药物的新时代。然而,蛋白质药物稳定性差、体内半衰期短且常具有免疫原性,极大限制了其临床治疗效果。目前,研究人员发展了多种策略改造蛋白质分子,其中以利用聚合物进行化学修饰发展最为迅速,并推动多种聚乙二醇修饰的蛋白质药物上市。天然多糖是构成生命体的大分子物质之一,与聚乙二醇类似,高相对分子质量的多糖可以赋予蛋白质类药物延长的半衰期、更高稳定性及更低免疫原性。另一方面,多糖修饰还可以提高蛋白质药物的靶向性、入胞能力,协同发挥多糖自身的抗凝、抗肿瘤和抗氧化等活性。本文对蛋白质药物的多糖修饰研究进展进行综述。

The rapid development of protein engineering and genetic engineering technology has ushered in a new era of protein drugs. However, the poor stability, short half-life in vivo and immunogenicity of protein drugs greatly limits their clinical efficacy. Among of the present strategies to overcome the drawbacks of protein molecules, the chemical modification with polymers has developed rapidly and led to successful approval of many pegylated proteins for sale. Natural polysaccharides are one of the biomacromolecules of the living organisms. Similar to PEG, the high molecular weight polysaccharides can endow protein drugs with prolonged half-lives, higher stability, and lower immunogenicity. On the other hand, polysaccharide modification can also improve protein drug targeting and cell membrane permeability, and synergistically exert the anticoagulant, anti-tumor and anti-oxidative activities of the polysaccharides. This review summarized the research progress of natural polysaccharides for modification of protein drugs.