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

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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.