||平井 剛, 新たな光反応性基で拡がる光親和性標識法のポテンシャル, ファルマシア, 10.14894/faruawpsj.54.10_953, 2018.10.
||平井 剛, 淺沼三和子, 土屋綾子, 袖岡幹子, 目的志向型ライブラリー戦略による両特異性プロテインホスファターゼ阻害剤の開発：コア構造の改変とユニークな阻害メカニズム, 有機合成化学協会誌, Vol.74, Page 532-540, 2016.05, Synthesis of a focused library (FL) is an efficient method to develop novel compounds regulating functions of specific enzymes. Compounds in a FL are composed of a common core structure with different building blocks. Herein, our design and synthesis of FLs based on selective inhibitors of dual-specificity protein phosphatases (DSPs) is summarized. A first generation FL having an acidic core structure extracted from a natural product, RK-682, does not contain a highly selective inhibitor for DSPs, and showed very weak activity at the cellular level, possibly due to poor cell membrane permeability. Upon building the second FL, the property of the core structure was modified from acidic to neutral. Construction of a second-generation FL (RE derivatives) having the enamine derivative of 3-acyltetronic acid as the core structure resulted in dramatic improvement of cell membrane permeability and inhibitory selectivity. As a result, VHR-selective RE12 and CDC25A/B-selective RE44 were discovered. Replacement of the side chain in RE12 afforded RE176, which showed more potent anti-proliferative activity against HeLa cells. Core structure modification from acidic to neutral also changed the mode of action of inhibitors. RE derivatives showed a non-competitive inhibition profile and interacts with a pocket adjacent to the active site of CDC25s..
||平井剛, 分子設計と有機合成による高機能型生物活性分子の創製：Physalin類のかご型構造の合成と生物機能, 有機合成化学協会誌.
||Go Hirai, Mimicking/Extracting Structure and Functions of Natural Products: Synthetic Approaches that Address Unexplored Needs in Chemical Biology, The Chemical Record (Personal Account).
||Go Hirai, Mikiko Sodeoka, Focused Library with a Core Structure Extracted from Natural Products and Modified: Application to Phosphatase Inhibitors and Several Biochemical Findings, Acc. Chem. Res..
||Go Hirai, Eisuke Ota, Motonari Sakai, Shigeru Nishiyama, Mikiko Sodeoka, C-Sialosides: Synthesis and Biological Activities（C-シアロシド結合を有する糖鎖アナログ：その合成と利用価値）, Trends in glycoscience and glycotechnology (Minireview).