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Development of Glycoconjugated Porphyrin Derivatives for Photodynamic Therapy

Research Project

Project/Area Number 13557211
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionNara Women's University

Principal Investigator

YANO Shiganobu  Nara Women's University, Grad.Sch.of Human Culture, Professor, 大学院・人間文化研究科, 教授 (60011186)

Co-Investigator(Kenkyū-buntansha) KAKUCHI Toyoji  北海道大学, 大学院・工学研究科, 教授 (80113538)
KINOSHITA Isamu  Osaka City Univ., Grad.Scho.of Science, Professor, 大学院・理学研究科, 教授 (80128735)
FUJIOKA Kenji  Formulation Research Lab., Sumitomo Pharmaceutical Research Div., Research Director, 製剤技術研究所, 研究所所長
小澤 俊彦  放射線医学総合研究所, 理事 (40160858)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsSugar / Photosensitizer / Photodynamic Therapy / PDT / ポルフィリン / クロリン / HeLa cell / S180 sarcoma cell / KLN205 squamous cel / 光線力学的療法 / バクテリオクロリン / 一重項酸素発生 / 光毒性 / HeLa細胞
Research Abstract

1.Novel Synthetic Strategy for Glycoconjuated Porphyrin Derivatives
In order to improve the yield of glycoconjugated porphyrin derivatives, especially for meta-substituted tetraphenyl porphyrin, Zn2+ ion template methodology had been developed. In addition, demonstrate the RP-TLC purification of glycoconjugated chlorin derivatives to remove concomitant by-product, glycoconjugated porphyrin and bacteriochlorin derivatives. So now glycoconjugated porphyrin and chlorin derivatives can be produced in applicable scale and purity in photodynamic therapy.
2.Estimation of Hydrophobicity of Glycoconjugated Porphyrin Derivatives
Hyrophobicity is fundamental characteristic for pharmakokinetics. We demonstrated the estimation of hydrophobicity of glycoconjugated porphyrin derivatives by means of reversed phase HPLC method. Significant sugedependent hydrophobicity was found clearly.
3.Cellular Uptake of Glycoconjugated Porphyrin Derivatives by HeLa cells
Prior to in vitro photocytotoxicity test, the cellular uptake amount of glycoconjugated porphyrin derivatives by HeLa cells was determined by means of fluorometry. The uptake amount significantly depended on sugar unit attached, However, no apprent correlation between hydrophobicity and cellular uptake was found.
4.In vitro Photocytotoxicity Test for Glycoconjugated Porphyrin Derivatives
Preliminary in vitro photocytotoxicity test was performed for glycoconjugated porphyrin derivatives which exerted higher amount of cellular uptake. Even though the photocytotoxicity was not connected to the cellular uptake amount, photocytotoxicity highly depended on sugar unit attached. These results suggest the possibility of glyco-regulation of photocytotoxicity in PDT.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All 2005 2004 2002 Other

All Journal Article (18 results) Publications (19 results)

  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa cells2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J. Photochem. Photobiol. B, Biology 78

      Pages: 7-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa Cells2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Photochem.Photobiol.B, Biology 78

      Pages: 7-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel Carbohydrate-Appended Metal Complexes for Potential Use in Molecular Imaging2005

    • Author(s)
      T.Storr
    • Journal Title

      Chem.Eur.J. 11

      Pages: 195-203

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa cells2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Photochem.Photobiol. B, Biology 78

      Pages: 7-15

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tetrakis(2-quinolinylmethyl)ethylenediamine(TQEN) as a new fluorescent sensor for zinc2005

    • Author(s)
      Y.Mikata
    • Journal Title

      Dalton Trans.

      Pages: 545-550

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Glucosamine-Dipicolylamine Conjugate of Tc-99m(I) and Re-189(I) for Use in Imaging and Therapy2005

    • Author(s)
      T.Storr
    • Journal Title

      Dalton Trans.

      Pages: 654-655

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hydrohobicity Parameters (Log P) og Glycoconjugated Porphyrins for Photodynamic Therapy Evaluated by Reversed Phase HPLC2004

    • Author(s)
      S.Hirohara
    • Journal Title

      J. Porphyrins and Phthalocyanines 8

      Pages: 1289-1292

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Porphyrins in HeLa cells2004

    • Author(s)
      S.Hirohara
    • Journal Title

      Photochem. Photobiol. 80

      Pages: 301-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hydrohobicity Parameters (Log P) of Glycoconjugated Porphyrins for Photodynamic Therapy Evaluated by Reversed Phase HPLC2004

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Porphyrins and Phthalocyanines 8(11)

      Pages: 1289-1289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Porphyrns in HeLa Cells2004

    • Author(s)
      S.Hirohara
    • Journal Title

      Photochem.Photobiol. 80

      Pages: 301-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hydrohobicity Parameters (Log P) og Glycoconjugated Porphyrins for Photodynamic Therapy Evaluated by Reversed Phase HPLC2004

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Porphyrins and Phthalocyanines 8

      Pages: 1289-1292

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Porphyrins in HeLa cells2004

    • Author(s)
      S.Hirohara
    • Journal Title

      Photochem.Photobiol. 80

      Pages: 301-308

    • Related Report
      2004 Annual Research Report
  • [Journal Article] meso-Tetraphenylporphyrin Having Hexamaltosyl and Decyl Chain as an Amphiphilic Photosensitizer toward Photodynamic Therapy2002

    • Author(s)
      A.Hamazawa
    • Journal Title

      Chem. Lett. 31

      Pages: 388-389

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Excitation Relaxation Dynamics and Molecular Dispersion of Maltohexaose-linked Tetraphenylporphyrins in Aqueous Solution2002

    • Author(s)
      Y.Arima
    • Journal Title

      Chem. Phys. Lett. 361

      Pages: 152-158

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of Novel Sugar Linked Photosensitizers for Photodynamic Therapy2002

    • Author(s)
      S.Yano
    • Journal Title

      Journal of Photoscience 9

      Pages: 174-177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] meso-Tetraphenylporphyrin Having Hexamaltosyl and Decyl Chain as an Amphiphilic Photosensitizer toward Photodynamic Therapy2002

    • Author(s)
      A.Hamazawa
    • Journal Title

      Chem.Lett. 31(3)

      Pages: 388-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Excitation Relaxation Dynamics and Molecular Dispersion of Maltohexaose-liked Tetraphenylporphyrins in Aqueous Solution2002

    • Author(s)
      Y.Arima
    • Journal Title

      Chem.Phys.Lett. 361

      Pages: 152-158

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of Novel Sugar Linked Photosensitizers for Photocynamic Therapy2002

    • Author(s)
      S.Yano
    • Journal Title

      Journal of Photoscience 9(2)

      Pages: 174-177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] A.Hamazawa: "Introduction of Chirality to the Remote, Open Face of a Metalloporphyrin through Coordination to the Metal of a Specially Designed Pendant Arm"Chem.Lett.. 32. 20-21 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Tanihara: "Synthesis of (μ-alkoxo)bis (μ-carboxylato)diruthenium complex having porphyrin moieties as a potential photo-harvesting functionality"Inorg.Chem.Commun.. 6. 447-450 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Mikata: "Detection of 1270 nm Emission from Singlet Oxygen and Photocytotoxic Property of Sugar-Pendant Fullerenes"Bioorg.Med.Chem.Lett.. 13. 3289-3292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Nakai: "Synthesis and Insulinomimetic Activities of Novel Mono- and Tetranuclear Oxovanadium(IV) Complexes with 3-Hydroxypyridine-2-carboxylic Acid"J.Inorg.Biochem.. 98. 105-112 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Araki: "Unprecedented Pendant Group Exchange of a Porphyrinato Platinum(II) in Benzonitrile"Chem.Lett.. 33(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] I.Brudzinska: "Synthesis, Structural Characterization, and Antitumor Activity of Palladium(II) Complexes Containing a Sugar Unit"Bioorg.Med.Chem.Lett.. 14(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Hamazawa: "meso-Tetraphenylporphyrin Having Hexa-maltosyl and Decyl Chain as an Amphiphilic Photosensitizer toword Photodynamic Therapy"Chem. Lett.. 31. 388-389 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Arima: "Excitation Relaxation Dynamics and Molecular Dispersion of Maltohexaose-linked Tetraphenylporphyrins in Aqueous Solution"Chem. Phys. Lett.. 361. 152-158 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Yano: "Mononuclear to Tetranuclear Structural Transformation in Vanadyl Complexes of 3-Hydroxypyridine-2-carboxylic Acid (H_2hpic)"Chem. Lett.. 31. 916-917 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Yano: "Development of Novel Sugar Linked Photosensitizers for Photodynamic The"Journal of Photoscience. 9. 174-177 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Yano: "Recent progress of glycoconjugated metal complexes"Bull. Chem. Soc. Jpn.. 75. 2097-2113 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Hamazawa: "Introduction of Chirality to the Remote, Open Face of a Metalloporphyrin through Coordination to the Metal of a Specially Designed Pendant Arm"Chem. Lett.. 32. 20-21 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 矢野重信: "新版 錯体化学 基礎と最新の展開"講談社サイエンティフク. 235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Hamazawa: "meso-Tetraphenylporphyrin Having Maltohexaosyl and Decyl Chain as an Amphiphilic Photosensitizer toward Photodynamic Therapy"Chem. Left.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Mikata: "Unprecedented Sugar-Dependent In Vivo Antitumor Activity of Carbohydrate-Pendant cis-Diamminedichloroplatinum(II)Complexes"Bioorg. Med. Chem. Lett. 11. 3045-3047 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Yano: "Structure of catena-Poly[[aqua(benzoato)(N, N'-dimethylformamide) calcium(II)]-μ-benzoato]"Acta. Crystallogr. E57. 488-490 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kawamoto: "Promotion of Radiation-Induced Formation of 8-Oxo-7, 8-dihydro-2' deoxyguanosine by Nitro 5-Deazaflavin Derivatives"Bioorg. Med. Chem. Lett. 11. 1745-1748 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Mikata: "Sugar-Pendant Diamines"J. Org. Chem. 66. 3783-3789 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Mikata: "NAD Models with Axial Chirality at the Carbamoyal Moiety : Superiority of the Quinolinium Ring System"J. Org. Chem.. 66. 1590-1599 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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