MT-2007, Protein Kinase C Inhibitor from Aetinomycetes Isolate No. 2007-18

방선균 분리주 No 2007-18이 생산하는 Protein Kinase C 저해물질, MT-2007

  • 안종석 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 박문수 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 박찬선 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 윤병대 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 민태익 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 안순철 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 오원근 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 이현선 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 윤병대 (한국과학기술연구원 유전공학연구소 미생물공학연구실)
  • Published : 1993.02.01

Abstract

During the screening of inhibitors against protein kinase CCPKC) and the bleb formation of K562 cell induced by phorbol ester from microbial secondary metabolites, MT-2007 was purified by solvent extraction, and chromatographic techniques from Actinomycetes isolate No. 2007-18. It showed completely suppression of bleb formation of K562 cell surface induced by phorbol 12.13dibutylate at the concentration of 503.9 11M and ICso on PKC was 31.4 11M. Its structure was postulated as lasalocid A sodium salt by physico-chemical properties and UV, IR. MS, IH-NMR.

미생물 대사산물로부터 phorbol ester에 의해 유도되는 K562 세포 표면의 소포형성 및 Protein kinase C(PKC)에 대한 저해제를 탐색하여 방선균 분리주 No.2007-18로 부터 용매추출 및 크로마토그래피의 기법을 이용하여 MT-2007을 분리하였다. MT-2007는 503.9MuM의 농도에서 phorbol 12,13-dibutylate에 의해 유도된 K562 세포표면의 bleb형성을 완전히 저해하였고, PKC 효소의 IC50 값은 31.4 MuM 이었다.

Keywords

References

  1. J. Biol. Chem. v.254 Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipid Takai,Y.;A.Kishimoto;Y.Iwasa;Y.Kawahaha;T.Mori;Y.Nishizuka
  2. Nature v.308 The role of protein kinase C in cell surface signal transduction and tumor promotion Nishizuka,Y.
  3. Science v.233 Studies and perspectives of protein kinase C Nishizuka,Y.
  4. Biochem. Biophys. Res. Comm. v.91 Unsaturated diacylglycerol as a possible messenger for the activation of calcium activated, phospholipid-dependent protein kinase system Takai,Y.;A.Kishimoto;U.Kikkawa;Y.Nishizuka
  5. J. Biol. Chem. v.255 Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol and its possible relation to phosphatidylinositol turnover Kishimoto,A.;Y.Takai;T.Morri;U.Kikkawa;Y.Nishizuka
  6. J. Biol. Chem. v.257 Direct activation of calcium-activated, phospholipid-dependent proteinkinase by tumor-promoting phorbol ester Castagna,M.;Y.Takai;K.Kaibuchi;K.Sano;U.Kikkawa;Y.Nishizuka
  7. C. Proc. Natl. Acad. Sci. USA v.80 Phorbol diester receptor copurifies with protein kinase Niedal,J.E.;L.J.Kuhn;G.R.Bandenberk
  8. Tips v.12 Signalling targets for anticancer drug development Powis,G.
  9. Biochem. Biophys. Res. Commun. v.158 Endothelin action inhibition by a protein kinase C inhibitor and involvement of phosphoinositols Sugiura,M.;T.Inagami;M.T.Gregory;A.Johns
  10. Prog. Lipid. Res. v.29 Lipid metabolism and signal transduction in endothelial cells Whatley,P.E.;G.A.Zimmerman;T.M.Mcintyre;S.M.Prescott
  11. Clin. Biochem. v.24 Growth factor and oncogene signalling pathways as targets for raditional drug development Powis,G.;A.Kozikowski
  12. Anti-Cancer Drug Design v.4 Protein kinase C a novel target for raditional anticancer drug design Gescher,A.;I.L.Dale
  13. J. Antibiot. v.41 Rapid screening method for inhibitors of protein kinase C Osada,H.;J.Magae;C.Watanabe;K.Isono
  14. J. Biol. Chem. v.263 Biochemical Characterization of rat brain protein kinase isozymes Huang,K.P.;F.L.Huang;H.Nakabayashi;Y.Yoshida
  15. Chem. Commun. v.1970 Structure of Antibiotic X-537A Westley,J.W.;R.H.Evans,Jr.;T.Williams;A.Stempel
  16. J. Antibiot. v.27 Isolation and structure determination of Lasalocid A Westley,J.W.;W.Benz;J.Donahue;R.H.Evans,Jr.;C.G.Scott;A.Stempel;J.Berger