Elucidation and control of iron homeostasis based on iron-sensing technology using N-oxide chemistry

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02110
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Hirayama Tasuku 岐阜薬科大学, 薬学部, 准教授 (10600207)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 鉄代謝 / スクリーニング / 蛍光プローブ

Outline of Final Research Achievements

Currently, drugs used in clinical practice to treat iron overload and iron deficiency are limited to chelating agents and iron supplements, respectively. This is also the case in cellular experiments, where there are very few useful chemical tools for iron research, including bioactive compounds that inhibit or promote iron uptake and efflux and fluorescent iron probes. In this study, we improved the N-oxide chemistry-based Fe(II) detection technology and developed a highly sensitive fluorescent probe for Fe(II) detection and a high-throughput intracellular Fe(II) assay system. Furthermore, we conducted HTS of a compound library using the high-throughput intracellular iron divalent assay system and found a new bioactive compound that modulate iron homeostasis.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、これまで検出することが困難であった細胞内鉄イオンを容易に可視化できるようにしたものであり、鉄研究において最大のネックであった鉄(II)イオンの選択的検出が可能になった。さらに、ハイスループットスクリーニングにより得た新たな鉄制御生理活性化合物は、鉄代謝を標的とした創薬シーズにもなりうることから、創薬研究の第一歩となる。