Development study of protein-protein interaction inhibitors through a diversity oriented fluorescence library approach

2019 Fiscal Year Final Research Report

• Project/Area Number: 18H05974
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Review Section: 0501:Physical chemistry, functional solid state chemistry, organic chemistry, polymers, organic materials, biomolecular chemistry, and related fields
• Research Institution: Nagoya University
• Principal Investigator: YAMAGUCHI Mayumi 名古屋大学, 創薬科学研究科, 特任助教 (80822345)
• Project Period (FY): 2018-08-24 – 2019-03-31
• Keywords: タンパク質間相互作用 / 蛍光物質 / ペプチド

Outline of Final Research Achievements

In this study, we tried to develop new protein-protein interaction inhibitors using diversity-oriented fluorescent library approach. First of all, we decided to use Kelch-like ECH-associated protein 1 (KEAP1) and NRF2 (NF-E2-related factor 2) as a model case, and designed and synthesized of analogs, which imitate C-terminus moiety of NRF2. These analogs were synthesized using solid phases peptide synthesis methods. Next, we designed and synthesized fluorescent substances, which have a xanthene structure.

Free Research Field

創薬科学

Academic Significance and Societal Importance of the Research Achievements

本研究はKEAP1/NRF2の新規タンパク質間相互作用阻害剤の開発を通して、あらゆるタンパク質間阻害剤開発におけるロールモデルの提案を行うものである。また、本研究によって得られる分子は、分子内の蛍光基の作用で、配列非改変型タンパク質を用いてin vitroの生物活性測定試験を行えるため、実際の生体内環境に近い形で構造活性相関研究ができる。この特性は、しばしば問題となるタンパク質レベルと細胞レベルでの生物活性測定試験の間に生じるギャップやin vitro/in vivo試験の間での生物活性測定試験のギャップを小さくし、効率的創薬リード創出ができる点で学術的意義及び社会的意義をもつ。