Target identification and mechanism of action of neoechinulin A

2017 Fiscal Year Final Research Report

• 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: KAMISUKI Shinji 麻布大学, 獣医学部, 講師 (30553846)
• 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
• 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

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.

Free Research Field

ケミカルバイオロジー