Synthesis of the variety nucleostide probes produced by synchronization of the biocatalyst and the palladium catalyst
| Project/Area Number |
24550193
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemistry related to living body
|
|---|
| Research Institution | Shibaura Institute of Technology |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 核酸代謝酵素 / チミジンホスホリラーゼ / 塩基部位交換反応 / RNAプローブ / 蛍光色素 / パラジウム触媒 / 薗頭カップリング / ヌクレオシド / RNA / プローブ / 合成 / 酵素合成 / 非天然ヌクレオシド / 有機溶媒効果 / ドッキングスタディー / イメージング |
|---|
| Outline of Final Research Achievements |
Thymidine phosphorylase (TP) is a unique metabolic control enzyme, TP can be used to change the nucleobase moiety of thymidine to a modified uracil substituted at the C5 position. The cross-coupling reaction by palladium catalyst such as Sonogashira coupling is convenient tool for introducing a fluorescent group at C5 position of uracil. We reasoned that TP and Pd catalyzed cross-coupling reaction could be used to easily obtain many different nucleosides containing a fluorescent group. We attempted to perform the base-exchange reaction by a hydrophobic modified uracil in buffer containing a polar organic solvent such as DMSO with TP. The reaction conversion was drastically enhanced as the concentration of DMSO increased up to 40 % (57 % conversion for U4C compound). Docking simulations using MF myPresto showed that uracil moiety of the substrate bound to the active site of TP, the fluorescent moiety linked to the C5 position of the uracil located outside the surface of the enzyme.
|
Report
(4 results)
Research Products
(14 results)
