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治疗蛋白革命性地改变了很多疾病的治疗结果,但体内活性低和快速的消除限制了其使用。糖工程是最近采用的一项新技术,通过改变与蛋白相连的糖类来改变蛋白质的药代动力学性质。这一技术已运用于促红细胞生成素,研制出一种促红细胞生成素高糖基化类似物DA(darbepoetinalfa),它含有2个附加的N-连接糖类。在血清中的半衰期增加了3倍,与重组人红细胞生成素比较,体内活性增加,提高了蛋白质的稳定性、可溶性,并且减少了免疫原性。本文讨论了糖基化对蛋白质性质的影响。
Therapeutic proteins have revolutionized the treatment of many diseases, but their low activity and rapid elimination in vivo limit their use. Sugar engineering is a recently introduced technology that alters the pharmacokinetic properties of proteins by altering the carbohydrate linked to the protein. This technique has been applied to erythropoietin to develop an erythropoietin hyperglycosylation analog DA (darbepoetinalfa) which contains two additional N-linked carbohydrates. The half-life in serum is increased three-fold, increasing in vivo activity compared to recombinant human erythropoietin, increasing protein stability, solubility, and reducing immunogenicity. This article discusses the effect of glycosylation on the nature of the protein.