2014 Fiscal Year Final Research Report
Development of short-step synthesis of probe molecules for accelerating target identification
| Project/Area Number |
25560402
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOTOKU Naoyuki 大阪大学, 大学院薬学研究科, 助教 (20362618)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 標的同定 / プローブ分子 / 生物活性物質 |
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| Outline of Final Research Achievements |
We developed short-step and concise synthetic method of affinity probe molecules derived from bioactive substances, through functional group-independent bond-forming reaction utilizing highly reactive species. The carbene species generated from 3-aryl-3-trifluoromethyldiazirine gave the best result, providing various reaction products efficiently. As a proof-of-concept study, we tried the direct derivatization of a bioactive natural product without anchoring functionality and the pulldown study. Only two-step reaction, the photo-crosslink reaction between diazirine and natural product followed by the Huisgen reaction, provided a biotinylated affinity probe. And the probe molecule was found to capture target protein of the parent compound, although relatively low efficiency and specificity were observed.
We also examined the cleavable site of the probe molecules to detect the specifically bound protein toward probe molecules, and a 1,2-diol unit was found to be the best among we tested.
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| Free Research Field |
天然物化学
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