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Microenviromental Analysis of Drug Binding Site on Albumin by Point-mutation and Using Probe

Research Project

Project/Area Number 06672146
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionKumamoto University

Principal Investigator

OTAGIRI Masaki  Faculty of Pharmaceutical Sciences, Kumamoto University Professor, 薬学部, 教授 (80120145)

Co-Investigator(Kenkyū-buntansha) IMAI Teruko  Kumamoto University. Research Asso., 薬学部, 教務員 (70176478)
IMAMURA Yorishige  Kumamoto University. Asso.Prof., 薬学部, 助教授 (30040314)
GOYA Shujiro  Kumamoto University. Professor, 薬学部, 教授 (50004560)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsAlbumin / Drug Binding Site / Probe / Point-mutation / Microenvironmental Analysis / Species Difference / 蛋白結合 / プローブ法 / 微環境解析 / 薬物結合サイト / N-B転移
Research Abstract

It is well-known that human serum albumin (HSA) has three specific binding sites for drugs, called site I,site II and site III.In addition, recent studies by X-ray crystal analysis indicated that the principal drug binding sites are located in subdomains IIA and IIIA.However, the drug binding sites on serum albumin for experimental animals such as rat, rabbit and dog have not yet been determined. Therefore, this investigation has been undertaken to study the characterization of these drug binding sites in the abovementioned animals. All the albumin examined have found to have at least two specific drug binding sites similar to human albumin using fluorescent probes. Further, using the different binding models assuming independent, competitive and anticooperative binding, these hypothesis were supported. The site I or site II on the albumin molecules seemed to be wide area consisting of subsites. However, unfortunately, we could not determine the microenvironmental analysis using the point-mutagenic techniques.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] H.Vorum,小田切優樹(他4名): "Calcium Ion Binding to Clinically Rehevant Chemical Modifications of Human Serum Albumin" Clinical Cheminstry. 41. 1654-1661 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 坂井利彰,小田切優樹(他1名): "Characterization of Binding Site of Uremic Toxins on Human Serum Albumin" Biological Pharmaceutical Bulletin. 18. 1755-1761 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 小田切優樹: "薬物の血清蛋白結合と相互作用" ファルマシア. 31. 989-991 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 坂井利彰,小田切優樹(他3名): "Mechanism of Stereoselective Serum Binding of Ketoprofen Following Hemodialysis" Journal of Pharmacogy & Experimental Therapeutics. 277. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山崎啓之,小田切優樹(他2名): "Characterization of Site I on Human Serum Albumin : Concept about the Structure of a Drug Binding Site" Biochemical Biophysica Acta. 1278. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 高村徳人,小田切優樹(他5名): "Mode of Interaction of Loop Diuretics with Human Serum Albumin and Characterization of Binding Site" Pharmaceutical Research. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 小田切優樹,末永綾香: "薬物間相互作用と医薬品の適正使用(伊賀立二監修)" 薬業時報社, 486 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Henrik.Vorum, Masaki Otagiri et al.: "Calcium Ion Binding to Clinically Relevant Chemical Modifications of Human Serum Albumin" Clinical Chemistry. 41. 1654-1661 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tosiaki Sakai, Masaki Otagiri et al.: "Charactarization of Binding Site of Uremic Toxins on Human Serum Albumin" Biological Pharmaceutical Bulletin. 18. 1755-1761 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaki Otagiti: "Serum Protein Binding of Drug and It's Interaction" Farmacia. 31. 989-991 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tosiaki Sakai, Masaki Otagiri et al.: "Mechanism of Stereoselective Serum Binding of Ketoprfen Following Hemodialysis" Journal of Pharmacology & Experimental Therapeutics. 277, (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Keishi Yamasaki, Masaki Otagiri et al.: "Charactarization of Site I on Human Serum Albumin : Concept about the Structure of a Drug Binding Site" Biochemical Biophysica Acta. 1278, (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norito Takamura, Masaki Otagiri et al.: "Mode of Interaction of Loop Diuretics with Human Serum Albumin and Charactarization of Binding Site" Phamaceutical Research. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masaki Otagiri, Ayaka Suenaga et al.: "Drug Interaction and Reasonable Use" Yakugyoujihousha. 486. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Vorum,小田切優樹(他4名): "Calcium Ion Binding to Clinically Relevant Chemical Modifications of Human Serum Albumin" Clinical Chemistry. 41. 1654-1661 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 坂井利彰,小田切優樹(他1名): "Characterization of Binding Site of Uremic Toxins on Human Serum Albumin" Biological Pharmaceutical Bulletin. 18. 1755-1761 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小田切優樹: "薬物の血清蛋白結合と相互作用" ファルマシア. 31. 989-991 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 坂井利彰,小田切優樹(他3名): "Mechanism of Stereoselective Serum Binding of Ketoprofen Following Hemodialysis" Journal of Pharmacopy & Experimantal Therapeuties. 277. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山崎啓之,小田切優樹(他2名): "Characterization of Site I on Human Serum Albumin : Concept about the Structure of a Drug Binding Site" Biochemica Biophysica Acta. 1278. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 高村徳人,小田切優樹(他5名): "Mode of Interaction of Loop Diuretics with Human Serum Albumin and Characterization of Binding Site" Pharmacentical Research. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小田切優樹,末永綾香: "薬物間相互作用と医薬品の適正使用(伊賀立二 監修)" 薬業時報社, 486 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小田切 優樹: "Interaction of benzothiadiazides with human serum albumin studied by dialysis and spectroscopic methods" Pharmaceutical Research. 11. 1452-1457 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 小田切 優樹: "Characterization of region Ic in site I on human serum albumin:Microenviromental analysis using fluorescence spectroscopy" Biological & Pharmaceutical Bulletin. 17. 1656-1662 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 小田切 優樹: "Calcium ion binding to clinically relevant chemical modifications of human serum albumin" Clinical Chemistry. 41(掲載予定). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 合屋 周次郎: "Fluorescence characteristics of methoxycoumarins as a novel fluorophores" Analytical Sciences. 11. 97-101 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 今村 順茂: "Catalytic properties of carboxyl reductase from rabbit kidney for acetohexamide and its analog" Bioorganic Chemistry. 22. 387-394 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 今井 輝子: "Effect of oral multiple-dose administration of anti-inflammatory flurbiprofen chimera drug on gastric lesion,other toxicities and disposition kinetics" Biological & Pharmaceutical Bulletin. 18. 140-147 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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