Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/27846
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    標題: Expression of beta-glucuronidase on the surface of bacteria enhances activation of glucuronide prodrugs
    作者: Cheng, C-M
    Chen, F. M.
    Lu, Y-L
    Tzou, S-C
    Wang, J-Y
    Kao, C-H
    Liao, K-W
    Cheng, T-C
    Chuang, C-H
    Chen, B-M
    Roffler, S.
    Cheng, T-L
    貢獻者: 藥學系
    關鍵字: Beta-Glucuronidase
    Autotransporter Protein Adhesin
    Bacteria-Directed Enzyme Prodrug Therapy
    Extracellular Activation
    Surface Display
    日期: 2013-05
    上傳時間: 2014-05-26 10:46:03 (UTC+8)
    出版者: Nature Publishing Group
    摘要: Extracellular activation of hydrophilic glucuronide prodrugs by p-glucuronidase (beta G) was examined to increase, the therapeutic, efficacy of bacteria-directed enzyme prodrug therapy (BDEPT). beta G was expressed on the surface of Escherichia coli by fusion to either the bacterial autotransporter protein Adhesin (membrane beta G (m beta G)/AIDA) or the lipoprotein (Ipp) outermembrane protein A (m beta G/Ipp). Both m beta G/AIDA and m beta G/Ipp were expressed on the bacterial surface, but only m beta G/AIDA displayed enzymatic activity. The rate of substrate hydrolysis by m beta G/AIDA-BL21 cells was 2.6-fold greater than by p beta G-BL21 cells, which express periplasmic beta G. Human colon cancer HCT116 cells that were incubated with m beta G/AIDA-BL21 bacteria were sensitive to a glucuronide prodrug (p-hydroxy aniline mustard beta-D-glucuronide, HAMG) with an half maximal inhibitory concentration (IC50) value of 226.53 +/- 45.4 M, similar to the IC50 value of the active drug (p-hydroxy aniline mustard, pHAM; 70.6 +/- 6.75 mu M), indicating that m beta G/AIDA on BL21 bacteria could rapidly and efficiently convert HAMG to an active anticancer agent. These results suggest that surface display of functional beta G on bacteria can enhance the hydrolysis of glucuronide prodrugs and may increase the effectiveness of BDEPT.
    關聯: Cancer Gene therapy, v.20 n.5, pp.276-281
    顯示於類別:[藥學系(所)] 期刊論文

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