Toguchi Shohei, Hirose Tomoyasu, Yorita Kazuko, Fukui Kiyoshi, Sharpless K Barry, Ōmura Satoshi, Sunazuka Toshiaki
Graduate School of Infection Control Sciences, Kitasato University.
Chem Pharm Bull (Tokyo). 2016 Jul 1;64(7):695-703. doi: 10.1248/cpb.c15-00867. Epub 2015 Dec 18.
In situ click chemistry is a target-guided synthesis approach for discovering novel lead compounds by assembling organic azides and alkynes into triazoles inside the affinity site of target biogenic molecules such as proteins. We report in situ click chemistry screening with human D-amino acid oxidase (hDAO), which led to the identification of a more potent hDAO inhibitor. The hDAO inhibitors have chemotherapeutic potential as antipsychotic agents. The new inhibitor displayed competitive inhibition of hDAO and showed significantly increased inhibitory activity against hDAO compared with that of an anchor molecule of in situ click chemistry.
原位点击化学是一种靶向引导的合成方法，通过在蛋白质等目标生物分子的亲和位点内将有机叠氮化物和炔烃组装成三唑来发现新型先导化合物。我们报道了用人D-氨基酸氧化酶（hDAO）进行的原位点击化学筛选，这导致鉴定出一种更有效的hDAO抑制剂。hDAO抑制剂作为抗精神病药物具有化疗潜力。与原位点击化学的锚定分子相比，新抑制剂对hDAO表现出竞争性抑制，并且对hDAO的抑制活性显著增加。
