Development of new methods for identification of novel targert proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05400
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Sakurai Kaori 東京農工大学, 工学(系)研究科(研究院), 教授 (50447512)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 標的タンパク質探索 / 化学プローブ / 金ナノ粒子 / アフィニティーラベリング / 天然物 / 光反応基

Outline of Final Research Achievements

Identification of target proteins are extremely important for understanding the molecular mechanisms of action of drugs and bioactive molecules, however, conventional methods are limited, and the establishment of a rational foundamental technology is urgently needed. In this study, we developed our original affinity-labeling probe design based on gold nanoparticles and applied it to various anticancer compounds, with the aim of establishing a versatile and comprehensive identification technology for target proteins. We designed probes applicable to various ligand molecules and developed a simple synthesis method, and prepared a variety of gold nanoparticles modified with natural product ligands and photoreactive groups. We also developed a novel reaction analysis method using multiwell plate-based screening and succeeded in rapidly evaluating affinity labeling reactions in electrophilic probes.

Free Research Field

生物有機化学・ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究では、中分子である天然物リガンドと異なる光反応基を修飾したプローブの簡便な合成調達を可能としたことから、アフィニティーラベリングによる天然物や医薬品シードの標的網羅同定のための新規基盤技術を創出した。また、アフィニティーラベリングに適した求電子基の探索法の開発により、ラベリング反応の効率化が可能となり、標的同定の飛躍的な加速化および一般化に貢献することができる。