Importance of Sialic Acid in Recombinant Thrombomodulin in Terms of Pharmacokinetics and Separation of Desialyzed Glycoprotein
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概要
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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.
- 1998-04-15
著者
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Koide T
Faculty Of Pharmaceutical Sciences Osaka University
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Koide Takashi
Tokyo Research Laboratories Kowa Co. Ltd.
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YOSHIZAKI HIDEO
Tokyo New Drug Research Laboratories II, Kowa Company, Ltd.
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KANDA Hiroyasu
日産化学工業株式会社中央研究所
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KIMATA Hideki
興和株式会社東京研究所
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Kimata H
Kowa Company Ltd. Tokyo
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Yoshizaki H
Tokyo New Drug Research Laboratories Ii Kowa Company Ltd.
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KIMATA Hideki
Tokyo Research Laboratories, Kowa Co., Ltd.
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YAMAMOTO Susumu
Tokyo Research Laboratories, Kowa Co., Ltd.
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Yoshizaki Hideo
Tokyo New Drug Research Laboratories Ii Kowa Company Ltd.
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EDANO Toshiyuki
Tokyo Research Laboratories, Kowa Co., Ltd.,
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KOSHI Tomoyuki
Tokyo Research Laboratories, Kowa Co., Ltd.,
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KUMAI Natuyo
Tokyo Research Laboratories, Kowa Co., Ltd.,
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HABATA Yuriko
Tokyo Research Laboratories, Kowa Co., Ltd.,
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MIZOGUCHI Toshimi
Tokyo Research Laboratories, Kowa Co., Ltd.,
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OHKUCHI Masao
Tokyo Research Laboratories, Kowa Co., Ltd.,
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Yamamoto S
Kagoshima Univ. Kagoshima Jpn
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Habata Yuriko
Tokyo Research Laboratories Kowa Co. Ltd.
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Kumai Natuyo
Tokyo Research Laboratories Kowa Co. Ltd.
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Ohkuchi Masao
Tokyo Research Laboratories Kowa Co. Ltd.
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Mizoguchi T
Tokyo Research Laboratories Kowa Co. Ltd.
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Edano T
Tokyo Research Laboratories Kowa Co. Ltd.
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Koshi T
Tokyo Research Laboratories Kowa Co. Ltd.
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Yamamoto Susumu
Tokyo Research Laboratories Kowa Company Ltd.
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Kimata Hideki
Tokyo Research Laboratories, Kowa Co. Ltd.
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