title: In Situ Click Chemistry for the Identification of a Potent D-Amino Acid Oxidase Inhibitor.
abstract: 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.
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University.
authors.forename: Shohei
authors.initials: S
authors.lastname: Toguchi
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yorita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukui
authors.forename: K Barry
authors.initials: KB
authors.lastname: Sharpless
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
mesh_terms: D057930:Click Chemistry; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D003605:D-Amino-Acid Oxidase