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

• Published in: Biological & Pharmaceutical Bulletin 2009/03/01, Vol.32(3), pp.440-443
• Main Authors: Cai, Gangming, Jiang, Mengjun, Zhang, Bo, Zhou, Yaoyuan, Zhang, Lianfen, Lei, Jianyong, Gu, Xiaobo, Cao, Guoxian, Jin, Jian, Zhang, Rongjun
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; asialoglycoprotein receptor; Cell Line; Female; galactosylated fusion interferon; Glycosylation; Hepatocytes - metabolism; Humans; In Vitro Techniques; Interferon alpha-2; Interferon-alpha - chemical synthesis; Interferon-alpha - chemistry; Interferon-alpha - pharmacology; Male; Mice; Mice, Inbred ICR; Protein Binding; Recombinant Fusion Proteins - chemical synthesis; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - pharmacology; Recombinant Proteins; Serum Albumin - chemistry; targeted drug; Tissue Distribution; Vesiculovirus - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.32.440

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 (p45%/g) and suggested that it also could be a good imaging agent of hepatic receptors.