Development of Molecular Probe Targeting on Glutathion Transferase

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  • Ito Mika
    Faculty of Pharmaceutical Sciences, Hokkaido University Nanomedical Engineering Laboratory, RIKEN
  • Shuto Satoshi
    Faculty of Pharmaceutical Sciences, Hokkaido University
  • Ito Yoshihiro
    Nanomedical Engineering Laboratory, RIKEN
  • Abe Hiroshi
    Faculty of Pharmaceutical Sciences, Hokkaido University Nanomedical Engineering Laboratory, RIKEN

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  • グルタチオントランスフェラーゼを標的とした分子プローブの開発
  • グルタチオントランスフェラーゼ オ ヒョウテキ ト シタ ブンシ プローブ ノ カイハツ

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Glutathione S-transferase (GST) are phase II enzymes that catalyze the nucleophilic attack of glutathione (GSH) to a wide range of hydrophobic and electrophilic compounds. GST is of high clinical interest in inflammation, pathophysiology and tumor drug resistance. In addition, GST is known to highly express in cancer cells. Therefore, we tried to develop new luminescent probes that can detect and image GST expression in living cells. Recently, we found that the electrophilic centre in the dinitrobenzenesulfonamide derivative is attacked by GSH and that this reaction is catalyzed by GST releasing the strong fluorophore. Based on this knowledge, we synthesized fluorescent probe, 19F MRI probe, and bioluminogenic probe. The fluorescent probe and kinetic parameters for purified GST were giving a rate enhancement of 106 compared with the nonenzymatic reaction. In addition, fluorescent probe successfully image GST in living cells. The fluorescent probe is potentially useful reagent for detection of GST activity in living cells.<br>19F MRI and bioluminogenic probes were synthesized using 4-acetyl-2-nitrobenzenesulfonyl group. 19F MRI probe exhibited a peak shift of 19F MRI signal and fluorescence enhancement in a bimodal way in response to GST activity. Bioluminogenic probe provided strong bioluminescence from GST activity. Moreover, both probes were successfully applied to the monitoring of GST expression in living E. coli cells. Successful detection of GST activity in living cells could be very useful for identifying tumor cells that overexpress GSTs.

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