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

1996 Fiscal Year Final Research Report Summary

Chemical identification of the binding sites for calcium antagonists in cardiac calcium channels and its application to developing new drugs

Research Project

Project/Area Number 07457543
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKumamoto University

Principal Investigator

NAKAYAMA Hitoshi  Kumamoto University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70088863)

Co-Investigator(Kenkyū-buntansha) KUNIYASU Akihiko  Kumamoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 教務員 (90241348)
ISHIZUKA Tadao  Kumamoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60176203)
HARADA Kumiko  Kumamoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (70150547)
NAKAYAMA Morio  Kumamoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60164373)
Project Period (FY) 1995 – 1996
Keywordscalcium antagonist / photoaffinity labeling / cardiac calcium channel / drug binding site / new compounds / drug design / synthesic chemistry
Research Abstract

In this project, we aim to reveal binding sites for calcium antagonists in cardiac calcium channels by photoaffinity labeling and the results are to be applied to design and synthesis of new drugs. New findings are as follows. (1) We identified the dihydropyridine sites in cardiac channel, which were identical to the skeletal muscle counterpart but some amino acids were substituted. The substitution can be interpreted to dominate the difference of binding affinity in two calcium channels. (2) Benzothiazepine binding sites were identified in segment 5 and 6 in repeat IV by photoaffinity labeling using azidobutyryl clentiazem with a rather small-sized photoprobe. The recent report by foreign investigaters where two labeled sites in repeat III and IV must be a wrong conclusion resulted from using a bulky photoprobe with long side chain. (3) We revealed the binding site of a new typed calcium antagonist of 1,4-benzothiazine structure 1 which is homologous to benzothiazepine 2 but the identified sites were different. The results can explain the pharmacological difference between two drugs. (4) Three dimentional structures of 1 and 2 are not ovelapped by x-ray crystallographic analysis. It suggests that we will design and synthesis of improved calcium antagonists which are derived from 2 as a lead compound.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Y.Hatanaka,et al.: "Synthesis of the nitro-substituted aryl diazirines" Chem.Pharm.Bull.42. 826-831 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakayama,et al.: "Chemical identification of the binding sites for calcium channel antagonists" Heterocycles. 42. 901-909 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Hatanaka,et al.: "Diazirine-based photoaffinity Labeling : Chemical approach to biological interfaces" Rev.Heteroatom Chem.14. 213-243 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakayama,et al.: "Identification of the binding sites for calcium channel antagonists" Japn.Heart J.37. ;643-650 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kuniyasu,et al.: "Identification of the 1,4-dihydropyridine binding sites within the α1 subunit of the cardiac calcium channels" Eur.J.Biochem.(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kuniyasu,et al.: "Identification of the binding region for a new calcium antagonist within the α1 subunit of calcium channels" J.Biol.Chem.(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Hatanaka, et al.: "Synthesis of the nitro-substituted ary diazirines." Chem.Pharm.Bull.42. 826-831 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakayama, et al.: "Chemical identification of the binding sites for calcium channel antagonists." Heterocycles. 42. 901-909 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Hatanaka, et al.: "Diazirine-based photoaffinity labeling : Chemical approach to biological interfaces." Rev.Heteroatom Chem.14. 213-243 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakayama and A.Kuniyasu: "Identification of the binding sites for calcium channel antagonists" Japn.Heart J.37. 643-650 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Kuniyasu, et al.: "Identification of the 1,4-dihydropyridine binding sites within the alpha1 of the cardiac calcium channels." Eur.J.Biochem.(in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Kuniyasu, et al.: "Identification of the binding region for a new calcium antagonist within the alpha1 subunit of the cardiac calcium channel" J.Biol.Chem.(in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-03-09  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi