『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=346353EID:346353, Map:0, LastModified:2019年3月5日(火) 11:13:46, Operator:[三木 ちひろ], Avail:TRUE, Censor:0, Owner:[福井 清], Read:継承, Write:継承, Delete:継承.
種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
招待 (推奨):
審査 (推奨): Peer Review [継承]
カテゴリ (推奨): 研究 [継承]
共著種別 (推奨): 国際共著 (徳島大学内研究者と国外研究機関所属研究者との共同研究) [継承]
学究種別 (推奨):
組織 (推奨): 1.徳島大学.先端酵素学研究所.次世代酵素学研究領域 (2016年4月1日〜) [継承]
著者 (必須): 1.加藤 有介 ([徳島大学.先端酵素学研究所.次世代酵素学研究領域])
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
2. (英) Hin Niyada (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
3.真板 宣夫 ([徳島大学.先端酵素学研究所.次世代酵素学研究領域])
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
4. (英) Thomas G. Ajit (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
5. (英) Kurosawa Sumire (日) 黒澤 すみれ (読) くろさわ すみれ
役割 (任意):
貢献度 (任意):
学籍番号 (推奨): **** [ユーザ]
[継承]
6. (英) Rojas Camilo (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
7.頼田 和子
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貢献度 (任意):
学籍番号 (推奨):
[継承]
8. (英) Slusher S. Barbara (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
9.福井 清 ([徳島大学])
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
10. (英) Tsukamoto Takashi (日) 塚本 尚 (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
題名 (必須): (英) Structural basis for potent inhibition of d-amino acid oxidase by thiophene carboxylic acids  (日)    [継承]
副題 (任意):
要約 (任意): (英) A series of thiophene-2-carboxylic acids and thiophene-3-carboxylic acids were identified as a new class of DAO inhibitors. Structure-activity relationship (SAR) studies revealed that small substituents are well-tolerated on the thiophene ring of both the 2-carboxylic acid and 3-carboxylic acid scaffolds. Crystal structures of human DAO in complex with potent thiophene carboxylic acids revealed that Tyr224 was tightly stacked with the thiophene ring of the inhibitors, resulting in the disappearance of the secondary pocket observed with other DAO inhibitors. Molecular dynamics simulations of the complex revealed that Tyr224 preferred the stacked conformation irrespective of whether Tyr224 was stacked or not in the initial state of the simulations. MM/GBSA indicated a substantial hydrophobic interaction between Tyr244 and the thiophene-based inhibitor. In addition, the active site was tightly closed with an extensive network of hydrogen bonds including those from Tyr224 in the stacked conformation. The introduction of a large branched side chain to the thiophene ring markedly decreased potency. These results are in marked contrast to other DAO inhibitors that can gain potency with a branched side chain extending to the secondary pocket due to Tyr224 repositioning. These insights should be of particular importance in future efforts to optimize DAO inhibitors with novel scaffolds.  (日)    [継承]
キーワード (推奨): 1. (英) Carboxylic Acids (日) (読) [継承]
2.X線結晶学 (X-ray crystallography) [継承]
3.D-アミノ酸酸化酵素 (D-amino acid oxidase) [継承]
4. (英) Dose-Response Relationship, Drug (日) (読) [継承]
5. (英) Enzyme Inhibitors (日) (読) [継承]
6. (英) Humans (日) (読) [継承]
7. (英) Models, Molecular (日) (読) [継承]
8.分子構造 (molecular structure) [継承]
9.構造活性相関 (structureactivity relationship) [継承]
10. (英) Thiophenes (日) (読) [継承]
発行所 (推奨): Elsevier (->組織[Elsevier Science]) [継承]
誌名 (必須): European Journal of Medicinal Chemistry (French Sociêtê de Chimie Thêrapeutique)
(pISSN: 0223-5234, eISSN: 1768-3254)

ISSN (任意): 1768-3254
ISSN: 0223-5234 (pISSN: 0223-5234, eISSN: 1768-3254)
Title: European journal of medicinal chemistry
Title(ISO): Eur J Med Chem
Publisher: Elsevier BV
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 159 [継承]
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(必須): 23 34 [継承]
都市 (任意):
年月日 (必須): 西暦 2018年 11月 5日 (平成 30年 11月 5日) [継承]
URL (任意):
DOI (任意): 10.1016/j.ejmech.2018.09.040    (→Scopusで検索) [継承]
PMID (任意): 30265959    (→Scopusで検索) [継承]
NAID (任意):
WOS (任意):
Scopus (任意): 2-s2.0-85053806498 [継承]
機関リポジトリ : 112839 [継承]
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被引用数 (任意):
指導教員 (推奨):
備考 (任意): 1.(英) Article.ELocationID: S0223-5234(18)30812-2  (日)    [継承]
2.(英) Article.ELocationID: 10.1016/j.ejmech.2018.09.040  (日)    [継承]
3.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]
4.(英) KeywordList.Keyword: Drug discovery  (日)    [継承]
5.(英) KeywordList.Keyword: Flavoenzyme  (日)    [継承]
6.(英) KeywordList.Keyword: Molecular dynamics  (日)    [継承]
7.(英) KeywordList.Keyword: Schizophrenia  (日)    [継承]
8.(英) KeywordList.Keyword: X-ray crystallography  (日)    [継承]

標準的な表示

和文冊子 ● Yusuke Kato, Niyada Hin, Nobuo Maita, Ajit G. Thomas, Sumire Kurosawa, Camilo Rojas, Kazuko YORITA, Barbara S. Slusher, Kiyoshi Fukui and Takashi Tsukamoto : Structural basis for potent inhibition of d-amino acid oxidase by thiophene carboxylic acids, European Journal of Medicinal Chemistry, Vol.159, 23-34, 2018.
欧文冊子 ● Yusuke Kato, Niyada Hin, Nobuo Maita, Ajit G. Thomas, Sumire Kurosawa, Camilo Rojas, Kazuko YORITA, Barbara S. Slusher, Kiyoshi Fukui and Takashi Tsukamoto : Structural basis for potent inhibition of d-amino acid oxidase by thiophene carboxylic acids, European Journal of Medicinal Chemistry, Vol.159, 23-34, 2018.

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