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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/30469

    標題: Reversibly Lipidized Interferon-alpha as an Anti-Hepatitis Drug
    作者: Wei-Chiang SHEN
    Liyun Yuan
    Jeffrey Wang
    貢獻者: University of Southern California School of Pharmacy
    Western University of Health Sciences School of Pharmacy
    關鍵字: reversible lipidization
    日期: 2008-07
    上傳時間: 2017-12-04 15:51:04 (UTC+8)
    摘要: Reversible aqueous lipidization (REAL) technologies involve the use of novel lipidizing reagents to modify peptides and proteins reversibly. Previously, we have demonstrated that REAL can increase plasma half-life, enhance oral absorption, prolong the therapeutic effects, and alter both biodistribution and elimination of peptide drugs. Recently, we have extended our investigation of REAL from peptides to proteins. Human interferon-alpha (INF), a 19.2KD protein containing two disulfide bonds (cys1-cys98;cys29-cys138), was reduced and modified with a reversible lipidization agent. The product of the lipidization, REAL-IFN, was homogenous, with four palmitoyl moieties linked to the four Cys residues in the protein molecule via reversible disulfide linkages. The far-UV circular dichroism (CD) spectrum of REAL-IFN was virtually overlapped with that of IFN, indicating that the IFN structure was not altered by the modification. After iv injection in mice at0.1 mg/kg of REAL-IFN activity was rapidly diminished to an undetectable level at 2 hours post IFN injection at the same dose. Unlike IFN or pegylated IFN, PAL-IFN was predominately localized in the liver of treated animals. Evidence suggested that IFN was slowly relesaed from REAL-IFN into bold circulation upon reduction of the disulfide bonds in vivo, possibly in the liver. Furthermore, the liver-targeting effect of PAL-IFN was demonstrated by the observation that the level 2'-5' oligoadenylate synthetase (OAS)expressed in the liver of mice treated with PAL-IFN was significantly higher than treatment with IFN. Therefore, REAL technology provides an alternative to pegylation for improving the therapeutic efficacy of IFN for the treatment of hepatitis.
    Appears in Collections:[藥理學院] 2008第五屆海峽化學、生物及材料研討會

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