Functional Group Non-selective Carbene Insertion Reaction as a Tool for Chemical Genetic Research
| Project/Area Number |
17510187
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Tohoku University (2006)
The Institute of Physical and Chemical Research (2005) |
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Principal Investigator |
KANOH Naoki Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院薬学研究科, 助教授 (40317293)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Small-molecule microarrays / Functioinal-group-independent immobilization / Photo-cross-linkin / Small-molecule affinity matrix / Reactivity of photo-generated carbene species |
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| Research Abstract |
1. Photo-Cross-Linked Small-Molecule Microarrays
During the first half of the term of project, the head investigator has optimized the photo-cross-linked small-molecule microarray platform; namely, he prepared and evaluated a variety of linkers connecting a small molecule and a glass slide, and found that a polyethylene glycol linker introduced on the glass slide via a urea linkage was optimal so far. In the latter half of the research period, he screened small-molecule ligands for a variety of proteins by using the optimized platform.
2. Evaluation of the Ractivity of Photo-Generated Aryltrifluoromethyl Carbene Species toward O-H and C-H Bonds within a Molecule
The head investigator has confirmed that (1) the photo-generated aryltrifluoromethyl carbene species was able to insert into not only an O-H bond but also unactivated C-H bonds within a low-molecular weight alcohol at the liquid state, and (2) the ratio of the C-H insertion products dramatically increased when the reaction was performed at the solid state. Furthermore, the structure of all the C-H and O-H insertion products was elucidated by using LC-MS/MS and LC-MS/MS/MS analyses.
3. Photo-Cross-Linked Small-Molecule Affinity Matrix
The head investigator has prepared both conventional-and photo-cross-linked small-molecule affinity matrices, and compared the amount of binding proteins bound to these affinity matrices. As a result, it was demonstrated that the photo-cross-linked small-molecule affinity matrix had the almost same capacity of recovering their binding protein with the conventional small-molecule affinity matrix in some cases.
Then, by using some biologically active small molecules that were stable under an amount of UV irradiation of 365 nm, he
prepared photo-cross-linked small-molecule affinity matrices, and obtained some previously-unknown targets for each small
molecule.
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Report
(3 results)
Research Products
(31 results)
