2009 Fiscal Year Final Research Report
The new method to identify small molecules binding proteins by usingmutants and genome sequences
Project/Area Number |
19380066
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bioproduction chemistry/Bioorganic chemistry
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Research Institution | Tokyo University of Science |
Principal Investigator |
菅原 二三男 Tokyo University of Science, 理工学部, 教授 (30192123)
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Project Period (FY) |
2007 – 2009
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Keywords | 受容体 / 結合タンパク質 / 遺伝子変異体 / ゲノム / ファージディスプレイ / QCM / 結合アミノ酸配列 |
Research Abstract |
The present study aimed at the identification of the action new and in vivo target protein of the establishment of the new medicine receptivity evaluation method that used gene mutation Drosophila melanogaster and CPT that used it. CPT-20-B connecting peptide (NSASRGGSQRGRGEH) is identified by using the T7 phage display method with crystal departure pendulum microbalance (QCM) device. This peptide sequencing showed each array and the homology of human HshnRNP A1 and Drosophila melanogaster DmHrb87F. CPT united from the bead pull-down examination that used HeLa cell meltable picture with HshnRNP A1. CPT made HshnRNP A1-GST united changing protein, did the QCM interaction analysis, and was HshnRNP A1 and was dissociation constant 82.7 nM. As a result of the microbial sensitivity test, by gene loss Drosophila melanogaster, two Hrb87FKG02089 and Hrb87FBG02743 that was the DmHrb87F gene mutant showed CPT high receptivity compared with the wild strain. Topo I has working that cancels a super-coil of plasmid DNA. This topology change was observed under CPT and the HshnRNP A1 existence. CPT obstructed the topo I revitalization as reported. Moreover, hnRNP A1 also similarly obstructed the topo I revitalization. In addition, CPT has improved the topo I active inhibition to HshnRNP A1 under both existence. HshnRNP A1 or DmHrb87F united from the above-mentioned result with CPT, and the possibility of adjusting the topo I revitalization was suggested.
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Research Products
(107 results)
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[Journal Article] Structure and activity relationship of monogalactosyl diacylglycerols, which selectively inhibited in vitro mammalian replicative DNA polymerase activity and human cancer cell growth.2009
Author(s)
Matsui Y, Hada T, Maeda N, Sato Y, Yamaguchi Y, Takeuchi T, Takemura M, Sugawara F, Sakaguchi K, Yoshida H, Mizushina Y.
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Journal Title
Cancer Lett 283(1)
Pages: 101-7
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[Journal Article] Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases.2009
Author(s)
Kimura T, Takeuchi T, Kumamoto-Yonezawa Y, Ohashi E, Ohmori H, Masutani C, Hanaoka F, Sugawara F, Yoshida H, Mizushina Y.
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Journal Title
Bioorg Med Chem 17(5)
Pages: 1811-6
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[Journal Article] Chlorogenic acid facilitates root hair formation in lettuce seedlings.2009
Author(s)
Narukawa M, Kanbara K, Tominaga Y, Aitani Y, Fukuda K, Kodama T, Murayama N, Nara Y, Arai T, Konno M, Kamisuki S, Sugawara F, Iwai M, Inoue Y.
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Journal Title
Plant Cell Physiol 50(3)
Pages: 504-14
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[Journal Article] Identification of trimannoside-recognizing peptide sequences from a T7 phage display screen using a QCM device.2009
Author(s)
Nishiyama K, Takakusagi Y, Kusayanagi T, Matsumoto Y, Habu S, Kuramochi K, Sugawara F, Sakaguchi K, Takahashi H, Natsugari H, Kobayashi S.
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Journal Title
Bioorg Med Chem 17(1)
Pages: 195-202
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[Journal Article] Effect of dehydroaltenusin-C12 derivative, a selective DNA polymerase alpha inhibitor, on DNA replication in cultured cells.2008
Author(s)
Kuriyama I, Mizuno T, Fukudome K, Kuramochi K, Tsubaki K, Usui T, Imamoto N, Sakaguchi K, Sugawara F, Yoshida H, Mizushina Y.
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Journal Title
Molecules 13(12)
Pages: 2948-61
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[Journal Article] Synthesis and biological activities of neoechinulin A derivatives: new aspects of structure-activity relationships for neoechinulin A.2008
Author(s)
Kuramochi K, Ohnishi K, Fujieda S, Nakajima M, Saitoh Y, Watanabe N, Takeuchi T, Nakazaki A, Sugawara F, Arai T, Kobayashi S.
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Journal Title
Chem Pharm Bull 56(12)
Pages: 1738-43
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[Journal Article] Identification of Small Molecule Binding Molecules by Affinity Purification Using a Specific Ligand Immobilized on PEGA Resin.2008
Author(s)
Kuramochi K, Miyano Y, Enomoto Y, Takeuchi R, Ishi K, Takakusagi Y, Saitoh T, Fukudome K, Manita D, Takeda Y, Kobayashi S, Sakaguchi K, Sugawara F.
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Journal Title
Bioconjug Chem 19(12)
Pages: 2417-26
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[Journal Article] Synthesis of Neoechinulin A and Derivatives.2008
Author(s)
Kuranochi K, Aoki T, Nakazaki A, Kamisuki S, Takeno M, Ohnishi K, Kimoto K, Watanabe N, Kamakura T, Arai T, Sugawara F, Kobayashi K.
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Journal Title
Synthesis 23
Pages: 3810-18
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[Journal Article] The specific inhibitory effect of demethoxydehydroaltenusin, a derivative of dehydroaltenusin, on mammalian DNA polymerase alpha.2008
Author(s)
Kuriyama I, Fukudome K, Kamisuki S, Kuramochi K, Tsubaki K, Sakaguchi K, Sugawara F, Yoshida H, Mizushina Y.
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Journal Title
Int J Mol Med 22(6)
Pages: 793-9
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[Journal Article] Efficient one-cycle affinity selection of binding proteins or peptides specific for a small-molecule using a T7 phage display pool.2008
Author(s)
Takakusagi Y, Kuramochi K, Takagi M, Kusayanagi T, Manita D, Ozawa H, Iwakiri K, Takakusagi K, Miyano Y, Nakazaki A, Kobayashi S, Sugawara F, Sakaguchi K.
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Journal Title
Bioorg Med Chem 16(22)
Pages: 9837-46
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[Journal Article] Downregulation of Tie2 gene by a novel antitumor sulfolipid, 3'-sulfoquinovosyl-1'-monoacylglycerol, targeting angiogenesis.2008
Author(s)
Mori Y, Sahara H, Matsumoto K, Takahashi N, Yamazaki T, Ohta K, Aoki S, Miura M, Sugawara F, Sakaguchi K, Sato N.
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Journal Title
Cancer Sci 99(5)
Pages: 1063-70
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[Journal Article] Syntheses and applications of fluorescent and biotinylated epolactaene derivatives: Epolactaene and its derivative induce disulfide formation.2008
Author(s)
Kuramochi K, Yukizawa S, Ikeda S, Sunoki T, Arai S, Matsui R, Morita A, Mizushina Y, Sakaguchi K, Sugawara F, Ikekita M, Kobayashi S.
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Journal Title
Bioorg Med Chem 16(9)
Pages: 5039-49
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[Journal Article] Hymenoic acid, a novel specific inhibitor of human DNA polymerase lambda from a fungus of Hymenochaetaceae sp.2008
Author(s)
Nishida M, Ida N, Horio M, Takeuchi T, Kamisuki S, Murata H, Kuramochi K, Sugawara F, Yoshida H, Mizushina Y.
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Journal Title
Bioorg Med Chem 16(9)
Pages: 5115-22
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[Journal Article] Coenzyme Q(10) as a potent compound that inhibits Cdt1-geminin interaction.2008
Author(s)
Mizushina Y, Takeuchi T, Takakusagi Y, Yonezawa Y, Mizuno T, Yanagi K, Imamoto N, Sugawara F, Sakaguchi K, Yoshida H, Fujita M.
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Journal Title
Biochim Biophys Acta 1780(2)
Pages: 203-13
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[Journal Article] Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases.2007
Author(s)
Nakamura R, Takeuchi R, Kuramochi K, Mizushina Y, Ishimaru C, Takakusagi Y, Takemura M, Kobayashi S, Yoshida H, Sugawara F, Sakaguchi K.
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Journal Title
Org Biomol Chem 5(24)
Pages: 3912-21
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[Journal Article] Structure-activity Relationships of Neoechinulin A Analogues with Cytoprotection against Peroxynitrite-induced PC12 Cell Death.2007
Author(s)
Kimoto K, Aoki T, Shibata Y, Kamisuki S, Sugawara F, Kuramochi K, Nakazaki A, Kobayashi S, Kuroiwa K, Watanabe N, Arai T.
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Journal Title
J Antibiot (Tokyo) 60(10)
Pages: 614-21
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[Journal Article] Effects of a new immunosuppressive agent, beta-SQAG9, in swine kidney transplantation.2007
Author(s)
Tanaka T, Kitamura H, Sahara H, Imai A, Itoh Y, Honma I, Sato E, Kobayashi K, Maeda T, Takenouchi M, Ohta K, Sugawara F, Sakaguchi K, Ando A, Inoko H, Sato N, Tsukamoto T.
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Journal Title
Transpl Immunol 18(1)
Pages: 67-71
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[Journal Article] Structure-activity relationship of a glycolipid, sulfoquinovosyl diacylglycerol, with the DNA binding activity of p53.2007
Author(s)
Iijima H, Kasai N, Chiku H, Takeuchi T, Kuramochi K, Hanashima S, Kobayashi S, Sugawara F, Sakaguchi K, Yoshida H, Mizushina Y.
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Journal Title
Int J Mol Med 19(1)
Pages: 41-8
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[Journal Article] Anti-tumor effects of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha.2007
Author(s)
Maeda N, Kokai Y, Ohtani S, Sahara H, Kuriyama I, Kamisuki S, Takahashi S, Sakaguchi K, Sugawara F, Yoshida H, Sato N, Mizushina Y.
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Journal Title
Biochem Biophys Res Commun 352(2)
Pages: 390-6
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[Presentation] 線虫ガレクチンLEC-6による糖鎖認識機構解明のための分子プローブの合成及びその評価2010
Author(s)
西山和沙, 山田篤, 草柳友恵, 松本勇記, 高草木洋一, 菅原二三男, 坂口謙吾, 小林進, 武内智春, 笠井献一, 夏苅英昭, 高橋秀依
Organizer
日本薬学会第130年会
Year and Date
2010-03-28
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[Presentation] YファミリーDNAポリメラーゼ選択的阻害剤:Penicilliol A, Penicilliol B2009
Author(s)
水品善之, 木村拓馬, 竹内倫文, 米澤裕子, 大橋英治, 大森治夫, 益谷央豪, 花岡文雄, 吉田弘美, 菅原二三男, 坂口謙吾
Organizer
第32回日本分子生物学会
Year and Date
2009-12-09
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[Presentation] トリマンノース由来の分子プローブの合成とQCM-PD-SAM法を用いた結合ペプチドの同定2009
Author(s)
西山和沙, 高草木洋一, 草柳友恵, 松本勇記, 羽生紫織, 倉持幸司, 菅原二三男, 坂口謙吾, 高橋秀依, 夏苅英昭, 小林進
Organizer
日本薬学会第129年会
Year and Date
2009-03-26
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[Presentation] T7 phage display法を用いたPFOS結合タンパク質の探索2008
Author(s)
岡戸真実, 宮野友香, 崎元一平, 志村聡美, 草柳友恵, 武内亮, 高草木香織, 松本勇記, 中崎敦夫, 竹内倫文, 倉持幸司, 高草木洋一, 太田慶祐, 三浦雅彦, 小林進, 菅原二三男, 坂口謙吾
Organizer
第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
Year and Date
2008-12-09
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[Presentation] 糖認識機能解明のための分子プローブの合成2008
Author(s)
西山和沙, 草柳友恵, 高草木洋一, 倉持幸司, 菅原二三男, 坂口謙吾, 武内智春, 笠井献一, 高橋秀依, 夏苅英昭, 小林進
Organizer
第55回有機合成化学協会関東支部シンポジウム
Year and Date
2008-05-09
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[Presentation] ニンニク由来の含硫黄物質群のDNAポリメラーゼ分子種選択的阻害活性とヒト癌細胞増殖抑制活性BMB20072007
Author(s)
西田真之, 羽田尚彦, 吉田英生, 木元貴士, 倉持幸司, 菅原二三男, 米澤裕子, 栗山磯子, 坂口謙吾, 吉田弘美, 水品善之
Organizer
第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
Year and Date
2007-12-11
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[Presentation] Down regulation of Tie-2 gene in vivo by novel anti-tumor agent SQAG targeting antiangionesis2007
Author(s)
Yoko Mori, Hiroeki Sahara, Kayo Matsumoto, Nobuaki Takahashi, Takayuki Yamazaki, Keisuke Ohta, Satoko Aoki, Masahiko Miura, Fumio Sugawara, Kengo Sakaguchi, Noriyuki Sato
Organizer
第66回日本癌学会学術総会
Year and Date
2007-10-03
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[Presentation] Identification of cyclosporin A binding protein CSBP that plays a critical role in hepatitis C virus genome replication2007
Author(s)
Hiroeki Sahara, Kengo Morohashi, Koichi Watashi, Yoko Mori, Kazuki Iwabata, Wataru Tsutae, Hiroki Miyashita, Kokichi Kikuchi, Kunitada Shimotohno, Kengo Sakaguchi, Noriyuki Sato, Fumio Sugawara
Organizer
第66回日本癌学会学術総会
Year and Date
2007-10-03
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