Target identification and mechanism of action of neoechinulin A
Project/Area Number |
15K01808
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biomolecular chemistry
|
Research Institution | Azabu University |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
SUGAWARA Fumio 東京理科大学, 理工学部, 教授 (30192123)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 天然物 / 生理活性物質 / 神経保護効果 / 活性窒素 / 神経細胞死 / ファージディスプレイ / 標的タンパク質 / ケミカルバイオロジー |
Outline of Final Research Achievements |
Neoechinulin A is an indole alkaloid that protects neuronal PC12 cells from cytotoxicity induced by the peroxynitrite generator SIN-1, but the target proteins and precise mechanism of action of neoechinulin A were unclear. In this study, we employed a phage display screen to identify proteins that bind directly with neoechinulin A. Our findings identified two proteins, chromogranin B and glutaredoxin 3, as candidate target binding partners for the compound. QCM analyses revealed that neoechinulin A displays high affinity for both chromogranin B and glutaredoxin 3. RNA interference-mediated depletion of chromogranin B decreased the sensitivity of PC12 cells against SIN-1. Our results suggested chromogranin B is a plausible target of neoechinulin A.
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Report
(4 results)
Research Products
(6 results)