糖加水分解酵素蛍光プローブ群の開発による新規迅速がんイメージング手法の確立
| Project/Area Number |
16F16109
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Research Field |
Chemical biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
浦野 泰照 東京大学, 大学院薬学系研究科(薬学部), 教授 (20292956)
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| Co-Investigator(Kenkyū-buntansha) |
RIVAS CHARLOTTE 東京大学, 薬学研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2016-10-07 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2018: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2017: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2016: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | sialidase / fluorescence / activation / cancer / self-immolative space / bacteria / Sialidase / Fluorescence activation / Lung cancer / Self-immolative space / Sialic acid substrate / Cancer imaging |
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| Outline of Annual Research Achievements |
Sialidases are members of a family of exoglycosidases specifically catalyzing the removal of sialic acid residues on the surface of exposed glycoconjugates. A novel fluorescence probe HMRef-S-Neu5Ac has been synthesised by incorporating a self-immolative spacer group between the sialic acid residue and the HMRef fluorophore to prevent hydrolysis via an acid-mediated pathway (i.e. in the absence of the target enzyme sialidase). First, kinetic measurements have shown the probe to have similar properties to that of a commercially available sialidase substrate, 4-MUNANA, demonstrating that the spacer group does not impede substrate recognition. Second, the stabilities of HMRef-S-Neu5Ac and a commercially avaiable 4MU-Neu5Ac were monitored over time at selected pHs of 2, 4, 6, 7.4 and 8. 4MU-Neu5Ac only showed significant instability at pH 2 where over the two-hour period fluorescence increased 5.6-fold. HMRef-S-Neu5Ac showed stability across all pHs within the two-hour experiment time. These experiments demonstrate that this probe is a better probe than 4MU-Neu5Ac due to its superior stability allowing for specificity for sialidase hydrolysis over acidic hydrolysis. The probe has been assessed in prostate cancer cells (LNCaP, DU145, PC3) which are reported to have significant levels of sialidase. Furthermore, some preliminary experiments of bacterial samples using this probe have been very positive and are currently under investigation.
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| Research Progress Status |
平成30年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
平成30年度が最終年度であるため、記入しない。
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Report
(3 results)
Research Products
(2 results)
