Preparation and Biological Evaluation of a Glycosylated Fusion Interferon Directed to Hepatic Receptors

• Cai Gangming

  School of Medicine and Pharmaceutics, Jiangnan University Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Jiang Mengjun

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Zhang Bo

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Zhou Yaoyuan

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Zhang Lianfen

  School of Medicine and Pharmaceutics, Jiangnan University

• Lei Jianyong

  School of Medicine and Pharmaceutics, Jiangnan University

• Gu Xiaobo

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Cao Guoxian

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine

• Jin Jian

  School of Medicine and Pharmaceutics, Jiangnan University

• Zhang Rongjun

  Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine School of Medicine and Pharmaceutics, Jiangnan University

抄録

The antiviral activity and biodistribution of a glycosylated fusion interferon directed to hepatic receptors were evaluated to determine whether its pharmaceutical concentration in the liver could be improved. The novel glycosylated fusion interferon, galactosyl-human serum albumin-interferon-α2b (G-HSA-IFN) was obtained from a long-term recombinant fusion protein (HSA-IFN) by covalent coupling with a bifunctional reagent, 2-imino-2-ethyloxymethy1-1-thiogalactose. There are about 24 thiogalactose residues in each G-HSA-IFN molecular on average. The antiviral activities of IFNα2b, HSA-IFN, and G-HSA-IFN were compared in a cytopathic effect inhibition assay with the WISH/VSV system in vitro, and the modification had little effect on its antiviral activity. Both G-HSA-IFN and HSA-IFN were labeled with ¹²⁵I and the radiochemical purity of ¹²⁵I-G-HSA-IFN was greater than 96%. ¹²⁵I-G-HSA-IFN bound to the asialoglycoprotein receptor (ASGP-R) on hepatic cells much more specifically than ¹²⁵I-HSA-IFN, with specific binding rates of 89.53% and 6.66%, respectively (p<0.01). Biodistribution research in mice showed that ¹²⁵I-G-HSA-IFN could concentrate effectively in the liver (>45%/g) and suggested that it also could be a good imaging agent of hepatic receptors.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 32 (3), 440-443, 2009

  公益社団法人 日本薬学会

キーワード

• asialoglycoprotein receptor
• galactosylated fusion interferon
• targeted drug

詳細情報

• CRID: 1390001204625052160
• NII論文ID: 110007122713
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.32.440
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 10166357
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10166357
• Web Site: http://www.jstage.jst.go.jp/article/bpb/32/3/32_3_440/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2009216330
• 本文言語コード: en
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