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2008 Fiscal Year Final Research Report

Exploring drug target peptides utilizing in silico analysis

Research Project

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Project/Area Number 19209026
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HIRATA Yukio  Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (50135787)

Co-Investigator(Kenkyū-buntansha) SHICHIRI Masayoshi  東京医科歯科大学, 医学部附属病院, 准教授 (10206097)
Project Period (FY) 2007 – 2008
Keywordsバイオインフォマティクス / ペプチドライブラリー / in silico / 生理活性ペプチド / ペプチド創薬 / ペプチド性ホルモン
Research Abstract

ヒトゲノム・cDNA資源データベースをバイオインフォマティクス解析して得られた情報をもとに数多くのペプチドを合成し、ペプチド創薬の観点から有用と推測されるものに焦点を絞って重点的に機能解析することによって生理活性因子候補因子からなるペプチドライブラリーを得た。ユニークな機能を有するいくつもの内因性ペプチド性リガンドを見出しつつあり、それらのヒト体液中での正確な分子存在様式を確認することと併行して、哺乳動物主要臓器における受容体の分布や生体内作用などを検討し、さらに物理化学的特性も含めて広範な解析を行った。我々の開発したこの新規ペプチド探索法は、従来の手法では発見できなかった内因性ペプチドホルモンを発見するには特に有効な手段であることが考えられた。

  • Research Products

    (34 results)

All 2010 2009 2008 2007 Other

All Journal Article (21 results) Presentation (9 results) Book (1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Release of salusin-β from human monocytes/macrophages2010

    • Author(s)
      Sato K, Fujimoto K, Koyama T, Shichiri M
    • Journal Title

      Reg Peptides 162

      Pages: 68-72

  • [Journal Article] Serum levels and urinary excretion of salusin-α in renal insufficiency2010

    • Author(s)
      Kimoto S, Sato K, Watanabe T, Suguro T, Koyama T, Shichiri M
    • Journal Title

      Reg Peptides 162

      Pages: 129-32

  • [Journal Article] Expression of prosalusin in human neuroblastoma cells2009

    • Author(s)
      Nakayama C, Shichiri M, Sato K, Hirata Y
    • Journal Title

      Peptides 30

      Pages: 1362-7

  • [Journal Article] Rifampicin as an oral angiogenesis inhibitor targeting hepatic cancers2009

    • Author(s)
      Shichiri M, Fukai N, Kono Y, Tanaka Y
    • Journal Title

      Cancer Res 69

      Pages: 4760-8

  • [Journal Article] Presence of immunoreactive salusin-β in human plasma and urine2009

    • Author(s)
      Sato K, Sato T, Susumu T, Koyama T, Shichiri M
    • Journal Title

      Reg Peptides 158

      Pages: 63-7

  • [Journal Article] Nitric oxide upregulates dimethylarginine dimethylaminohydrolase-2 via cyclic GMP induction in endothelial cells2008

    • Author(s)
      Sakurada M, Shichiri M, Imamura M, Azuma H, Hirata Y
    • Journal Title

      Hypertension 52

      Pages: 903-9

  • [Journal Article] Aldosterone induces superoxide generation via Rac1 activation in endothelial cells2008

    • Author(s)
      Iwashima F, Yoshimoto T, Minami I, Sakurada M, Hirono Y, Hirata Y
    • Journal Title

      Endocrinology 149

      Pages: 1009-14

  • [Journal Article] Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages2008

    • Author(s)
      Miyake A, Murata Y, Okazawa H, Ikeda H, Niwayama Y, Ohnishi H, Hirata Y, Matozaki T
    • Journal Title

      Genes to Cells 13

      Pages: 209-19

  • [Journal Article] Aldosterone-stimulated SGK1 activity mediates profibrotic signaling in the mesangium2008

    • Author(s)
      Terada Y, Kuwana H, Kobayashi T, Okado T, Suzuki N, Yoshimoto T, Hirata Y, Sasaki S
    • Journal Title

      J Am Soc Nephrol 19

      Pages: 298-309

  • [Journal Article] Chronic osmotic stimuli increase salusin-β-like immunoreactivity in the rat hypothalamo-neurohypophyseal system : possible involvement of salusin-β on [Ca^<2+>]_i increase and neurohypophyseal hormone release from the axon terminals2008

    • Author(s)
      Saito T, Dayanithi G, Saito J, Onaka T, Urabe T, Watanabe TX, Hashimoto H, Yokoyama T, Fujihara H, Yokota A, Nishizawa S, Hirata Y, Ueta Y
    • Journal Title

      J Neuroendocrinol 20

      Pages: 207-19

  • [Journal Article] Biosynthesis and secretion of salusin-α from human cells2008

    • Author(s)
      Sato K, Koyama T, Shichiri M
    • Journal Title

      Peptides 29

      Pages: 2203-7

  • [Journal Article] Serum salusin-α levels are decreased and correlated negatively with carotid atherosclerosis in essential hypertensive patients2008

    • Author(s)
      Watanabe T, Suguro T, Sato K, Koyama T, Nagashima M, Kodate S, Hirano T, Adachi M, Shichiri M, Miyazaki A
    • Journal Title

      Hypertens Res 31

      Pages: 463-8

  • [Journal Article] Impact of salusin-α and-β on human macrophage foam cell formation and coronary atherosclerosis2008

    • Author(s)
      Watanabe T, Nishio K, Kanome T, Matsuyama TA, Koba S, Sakai T, Sato K, Hongo S, Nose K, Ota H, Kobayashi Y, Katagiri T, Shichiri M, Miyazaki A
    • Journal Title

      Circulation 117

      Pages: 638-48

  • [Journal Article] Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension : the possible role of local renin-angiotensin system2007

    • Author(s)
      Hirono Y, Yoshimoto T, Suzuki N, Sugiyama T, Sakurada M, Takai S, Kobayashi N, Shichiri M, Hirata Y
    • Journal Title

      Endocrinology 148

      Pages: 1688-96

  • [Journal Article] Systemic distribution of salusin expression in the rats2007

    • Author(s)
      Suzuki N, Shichiri M, Akashi T, Sato K, Sakurada M, Hirono Y, Yoshimoto T, Koyama T, Hirata Y
    • Journal Title

      Hypertens Res 30

      Pages: 1255-62

  • [Journal Article] Reply to 'Salusins ; newly identified bioactive peptides with hemodynamic and mitogenic activities'2007

    • Author(s)
      Shichiri M
    • Journal Title

      Nature Med 13

      Pages: 661-2

  • [Journal Article] Defective expression of prohormone convertase 1/3 in silent corticotroph adenoma2007

    • Author(s)
      Tateno T, Izumiyama H, Doi M, Akashi T, Ohno K, Hirata Y
    • Journal Title

      Endocrine J 54

      Pages: 777-82

  • [Journal Article] Differential gene expression in adrenocorticotropin (ACTH)-secreting and non-functioning pituitary tumors2007

    • Author(s)
      Tateno T, Izumiyama H, Doi M, Yoshimoto T, Shichiri M, Inosita M, Oyama K, Yamada S, Hirata Y
    • Journal Title

      Eur J Endocrinol 157

      Pages: 717-24

  • [Journal Article] Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high-fat-induced obese mice2007

    • Author(s)
      Tsuchiya K, Sakai H, Suzuki N, Iwashima F, Yoshimoto T, Shichiri M, Hirata Y
    • Journal Title

      Endocrinology 148

      Pages: 4548-56

  • [Journal Article] Aldosterone as a cardiovascular risk hormone2007

    • Author(s)
      Yoshimoto T, Hirata Y
    • Journal Title

      Endocrine J 54

      Pages: 359-70

  • [Journal Article] MARCH-X1, a novel transmembrane ubiquitin ligase implicated in ubiquitin-dependent protein sorting in developing spermatids2007

    • Author(s)
      Morokuma Y, Nakamura N, Kato A, Notoya M, Yamamoto Y, Sakai Y, Fukuda H, Yamashina S, Hirata Y, Hirose S
    • Journal Title

      J Biol Chem 282

      Pages: 24806-15

  • [Presentation] NO upregulates dimethylarginine dimethylaminohydrolase-2 via cGMP induction in endothelial cells2008

    • Author(s)
      Sakurada M, Shichiri M, Imamura M, Azuma H, Hirata Y
    • Organizer
      The 22th Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      20080600
  • [Presentation] Defective expression of prohormone convertase 4 in pleural solitary fibrous tumor causing non-islet cell tumor hypoglycemia (NICTH)2008

    • Author(s)
      Tani Y, Tateno T, Izumiyama H, Doi M, Yoshimoto T, Hirata Y
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20080600
  • [Presentation] Metabolic syndrome is associated with endothelial dysfunction : Important roles of hyperinsulinemia and Hypertension2008

    • Author(s)
      Tsuchiya K, Nakayama C, Iwashima F, Sakai H, Yoshimoto T, Hirata Y
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20080600
  • [Presentation] Differential gene expression of somatostatin receptor (SSTR) subtype and dopamine type 2 receptor (D2R) in adrenocorticotropin (ACTH)-secreting and non-functioning pituitary tumors2008

    • Author(s)
      Tateno T, Izumiyama H, Doi M, Yoshimoto T, Oyama K, Yamada Y, Hirata Y
    • Organizer
      The Endocrine Society's Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20080600
  • [Presentation] In silico 探索法による循環調節因子サリューシンの同定と新たな展開2007

    • Author(s)
      七里眞義, 平田結喜緒
    • Organizer
      第11回日本心血管内分泌代謝学会 シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20071100
  • [Presentation] Possible involvement of small GTP-binding protein, Rac-1, in aldosterone-stimulated superoxide production in endothelial cells2007

    • Author(s)
      Iwashima F, Yoshimoto T, Sakurada M, Minami I, Hirata Y
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20070600
  • [Presentation] Differential gene expression in adrenocorticotropin (ACTH)-secreting and non-functionong pituitary tumors2007

    • Author(s)
      Tateno T, Izumiyama H, Doi M, Yoshimoto T, Oyama K, Yamada S, Hirata Y
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20070600
  • [Presentation] Endothelial dysfunction in patients with Cushing's syndrome and acromegaly2007

    • Author(s)
      Tsuchiya K, Yoshimoto T, Nakayama C, Iwashima F, Sakai H, Hirata Y
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20070600
  • [Presentation] Effects of telmisartan on endothelial function and arterial stiffness in diabetic patients with hypertension2007

    • Author(s)
      Wago T, Tsuchiya K, Kouyama R, Izumiyama H, Doi M, Yoshimoto T, Hirata Y
    • Organizer
      The 17th European Meeting on Hypertension
    • Place of Presentation
      Milano, Italy
    • Year and Date
      20070600
  • [Book] 「In silico ペプチド探索」遺伝子医学MOOK第8号「ペプチドと創薬」(寒川賢治, 南野直人, 編)2007

    • Author(s)
      七里眞義
    • Total Pages
      63-67
    • Publisher
      メディカルドウ
  • [Patent(Industrial Property Rights)] サリューシンをターゲットとする動脈硬化性疾患の治療剤及び検出薬

    • Industrial Property Number
      特願2007-127131
  • [Patent(Industrial Property Rights)] サリューシン-βを含む医薬

    • Industrial Property Number
      特願2007-279006
  • [Patent(Industrial Property Rights)] サリューシン-βのアンタゴニストを含む心筋虚血再灌流傷害抑制剤法

    • Industrial Property Number
      特願2009-064588

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Published: 2011-06-18   Modified: 2016-04-21  

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