title: Preparation and biological evaluation of a glycosylated fusion interferon directed to hepatic receptors.
abstract: 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-alpha2b (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 IFNalpha2b, 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.
authors.affiliation: School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, PR China.
authors.forename: Gangming
authors.initials: G
authors.lastname: Cai
authors.forename: Mengjun
authors.initials: M
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yaoyuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lianfen
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianyong
authors.initials: J
authors.lastname: Lei
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Gu
authors.forename: Guoxian
authors.initials: G
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Rongjun
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006031:Glycosylation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000737:chemistry; D014018:Tissue Distribution; D018116:Vesiculovirus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin