『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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登録内容 (EID=188346)

EID=188346EID:188346, Map:0, LastModified:2009年11月10日(火) 15:37:37, Operator:[山田 美緒], Avail:TRUE, Censor:0, Owner:[宇都 義浩], Read:継承, Write:継承, Delete:継承.
種別 (必須): 国際会議 [継承]
言語 (必須): 英語 [継承]
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カテゴリ (推奨): 研究 [継承]
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学究種別 (推奨): 博士後期課程学生による研究報告 [継承]
組織 (推奨): 1.生命情報工学 (2006年4月1日〜2016年3月31日) [継承]
著者 (必須): 1. (英) Nakashima Hitomi (日) (読)
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[継承]
2. (英) Ikkyu Kazuhiro (日) (読)
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[継承]
3. (英) Nakashima Kouichiro (日) (読)
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[継承]
4. (英) Sano Keiichiro (日) (読)
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[継承]
5.宇都 義浩 ([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.応用生物資源学分野]/[徳島大学.生物資源産業学部.生物資源産業学科.応用生命講座])
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[継承]
6.中田 栄司
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7.永澤 秀子 (岐阜薬科大学/->個人[紺世 秀子])
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[継承]
8. (英) Sugimoto Hiroshi (日) (読)
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[継承]
9. (英) Shiro Yoshitsugu (日) (読)
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[継承]
10. (英) Nakagawa Yoshinori (日) (読)
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11.堀 均
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[継承]
題名 (必須): (英) Design of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety  (日)    [継承]
副題 (任意):
要約 (任意): (英) Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate limiting step of L-Tryptophan (L-Trp) catabolism in the kynurenine pathway. IDO expresses in many neoplasms, and play a role in immunosuppression. IDO is activated only reductive or hypoxic conditions, because the heme iron of active site is easily oxidized to its inactive form. Hypoxic neoplastic cells indicate chemo- and radioresistances and also cause neoplasm' progression, invasion and metastasis. Previously we focused to the mode of activation of IDO only in hypoxic and reductive condition to design hypoxia-targeting IDO hybrid inhibitors, which constituted an IDO inhibitor 1-methyl-tryptophan (1MT) and hypoxic cytotoxin tirapazamine (TPZ), such as TX-2236, TX-2235, TX-2228 and TX-2234. They were good hypoxia-targeting IDO inhibitors. 1MT-TPZ hybrids inhibited IDO uncompetitively. Thus, it suggests that 1MT-TPZ hybrids were able to bind the only enzyme-substrate complex, not to bind the active site. In this study, we present here the novel design and syntheses of hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety without inhibitor 1MT such as L-Trp-TPZ hybrids 1 (n = 4, monoxide), 2 (n = 4, dioxide), 3 (n = 5, monoxide), and 4 (n = 5, dioxide). These L-Trp-TPZ hybrids were synthesized from 3-chlorinated TPZ monoxide with various length alkyldiamines to give the corresponding amine derivatives, which were conjugated with Boc-L-Trp to give the L-Trp-TPZ monoxide hybrids 1 and 3. L-Trp-TPZ dioxide hybrids 2 and 4 were also synthesized from the corresponding TPZ-dioxide trifluoroacetamide intermediates. L-Trp-TPZ hybrids were good competitive inhibitors of IDO. Thus, it suggests that these L-Trp-TPZ hybrids were able to bind the active site. In conclusion, we discovered IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety. Additionally we are under evaluation of their hypoxic cytotoxicity to develop hypoxia-targeting IDO hybrid inhibitors as our final goal.  (日)    [継承]
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誌名 (必須): (英) ISOTT2008 (2008 International Society on Oxygen Transport to Tissue Conference) (日) (読)
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[継承]
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都市 (必須): 札幌 (Sapporo/[日本国]) [継承]
年月日 (必須): 西暦 2008年 8月 6日 (平成 20年 8月 6日) [継承]
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標準的な表示

和文冊子 ● Hitomi Nakashima, Kazuhiro Ikkyu, Kouichiro Nakashima, Keiichiro Sano, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshinori Nakagawa and Hitoshi Hori : Design of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety, ISOTT2008 (2008 International Society on Oxygen Transport to Tissue Conference), Sapporo, Aug. 2008.
欧文冊子 ● Hitomi Nakashima, Kazuhiro Ikkyu, Kouichiro Nakashima, Keiichiro Sano, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshinori Nakagawa and Hitoshi Hori : Design of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety, ISOTT2008 (2008 International Society on Oxygen Transport to Tissue Conference), Sapporo, Aug. 2008.

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Number of session users = 8, LA = 0.48, Max(EID) = 361932, Max(EOID) = 968397.