文章基本信息

标题：Importance of Sialic Acid in Recombinant Thrombomodulin in Terms of Pharmacokinetics and Separation of Desialyzed Glycoprotein
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作者：Toshiyuki EDANO ; Tomoyuki KOSHI ; Hideo YOSHIZAKI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：4
页码：382-385
DOI：10.1248/bpb.21.382
出版社：The Pharmaceutical Society of Japan
摘要：Recombinant glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM) expressed in mouse C-127 cells has potent antithrombotic activity available as an anticoagulant. GAG-UTM, a glycoprotein with sialic acid, was investigated regarding the influence of the terminal sialic acid on its pharmacokinetics upon rapid intravenous injection in rat. Asialo GAG-UTM desialated by neuraminidase was cleared rapidly from plasma. Sialyzed GAG-UTM, a sialyzed asialo GAG-UTM with α-2, 6-sialyltransferase, containing sialic acid similarly to native sialo GAG-UTM, had only a short half-life in plasma, suggesting that the binding site of sialic acid on galactose was not only sialyzed with α-2, 6-sialyltransferase but also with 2, 3-sialyltransferase. Asialo GAG-UTM with oxidized terminal galactose, however, had a long half-life. These results suggest that terminal sialic acid may be important to the pharmacokinetics of GAG-UTM; therefore, an analysis of asialo GAG-UTM became significant for quality control. In order to analyze sialo-and asialo-types in the early stage of purification, we investigated separation and analysis methods for both types and found a suitable sample of each : RCA-120-Agarose column for separation and ELISA using anti-thrombomod-ulin antibody and RCA lectin for analysis.
关键词：thrombomodulin;plasma clearance;sialyltransferase;galactose oxidase;RCA lectin