• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Combinatorial Synthesis of Transition State Mimetic Inhibitor Using Asymmetric Aldol, Reaction

Research Project

Project/Area Number 13672211
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionOsaka University

Principal Investigator

AKAJI Kenichi  Osaka University, Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (60142296)

Co-Investigator(Kenkyū-buntansha) KAWAKAMI Toru  Osaka University, Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (70273711)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsAsvmmetirc aldol reaction / Enzyme inhibitor / Protease / Transition state mimetic / HTLV-1 / Solid phase synthesis / library / コンビナトリアル合成
Research Abstract

An efficient method has been developed for the first solid phase synthesis of HTLV 1 protease inhibitors that contain hydroxyethylamine isostere as transitionslate mimetic. The synthetic procedure was designed to allow the evaluation of stereostmctureactivity relationships at the scissile site. All the possible configurations at the hydroxy and side chainbearing asymmetric centers of the isostere were constructed by an esterderived asymmetric aldol reaction. Each inhibitor containing the isostere backbone was synthesized on solid support using the newly developed succinate ester linker. The configuration at the hydroxy and side chainbearing asymmetric center showed remarkable effects on the inhibitory activity. The K_i value changed with approximately two orders of magnitude. This approach enables an efficient preparation of the inhibitors containing a transitionstate mimetic

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] K.Teruya, T.Kawakami, K.Akaji, S.Aimoto: "Total synthesis of [L40I, C90A, C109A]-human T'cell leukemia virus type 1 protease"Tetrahedron Letters. 43. 1487-1490 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Akaji, K.Teruya, S.Aimoto: "Stereoselective synthesis and evaluation of HTLV-1 protease inhibitors"Peptide Science 2002. 2002. 37-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Akaji, K.Teruya, S.Aimoto: "Solid-phase synthesis of HTLV-1 protease inhibitors containing hydroxyethylamine dipeptide isostere"Journal of the Organic Chemistry. 2003(In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K,Teniya, T,Kawakami, K,Akaji, S,Aimoto: "Total Synthesis of [L40I, C90A, C109A]-human T-cefl leukemia virus type 1 protease"Tetrahedron Lett.. 43. 1487-1490 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K,Akaji, K,Teraya, S,Aimoto: "Stereoselective synthesis and evaluation of HTLV-1 protease inhibitors"Peptide Scaerice 2002. 37-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K,Akaji, K,Teruya, S,Aimoto: "Solid-phase synthesis of HTLV-1 protease Inhibitors containing hydroxyethylamine dipeptide isostere"J. Org. Chem.. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Teruya, T.Kawakami, K.Akaji, S.Aimoto: "Total synthesis of [L40I, C9OA, C109A]-human T-cell leukemia virus type 1 protease"Tetrahedron Letters. 43. 1487-1490 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Akaji, K.Teruya, S.Aimoto: "Stereoselective synthesis and evaluation of HTLV-1 protease inhibitors"Peptide Science 2002. 2002(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Teruya, T.Kawakami, K.Akaji, S.Aimoto: "Synthesis of [L40I, C90A, C109A]-human T-cell leukemia virus-type 1 protease"Tetrahedron Letters. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kawakami, K.Akaji, S.Aimoto: "Peptide bond formation mediated by 4,5-dimethoxy-2-mercaptobenzylamine after periodate oxidation of the N-terminal serine residue"Organic Letters. Vol3, No9. 1403-1405 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi