Purification and Chemical Identification of the Inhibitor on Bleb Formation of K562 Cell Induced by Phorbol Ester from Actinornycetes Isolate No. 1882-5

방선균 분리주 No. 1882-5로부터 Phorbol Ester에 의해 유도되는 K562 Cell의 소포형성을 억제하는 물질의 분리와 동정

  • 안종석 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 안순철 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 박문수 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 김보연 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 민태익 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 이현선 (한국과학기술연구원 유전공학연구소 미생물공학실) ;
  • 오원근 (한국과학기술연구원 유전공학연구소 미생물공학실)
  • Published : 1992.10.01

Abstract

We isolated Actinomycetes strain No. 1882-5, which produces the inhibitor on the bleb formation of K562 cell induced by phorbol ester, from soil sample. Through solvent extraction, Amberlite XAD-4, silica and Lobar low pressure LC, antifungal antibiotic MT 1882-1 and bleb forming inhibitor MT 1882-II were purified from strain No. 1882-5. MT 1882-1 was identified as piericidin $A_{1}$($C_{25}H_{37}0_4N$, M.W. 415) and MT 1882-11 as glucopiericidin A($C_{31}H_{47}0_9N$, M.W. 577) from the analysis of physico-chemical properties and UV, $^1H-NMR$, $^13C-NMR$, and mass spectra of these compounds.

Phorbol ester에 의해 유도되는 K562 cell의 소포 형성을 저해하는 물질을 생산하는 방선균 분리주 No.1882-5를 토양으로부터 분리하였다. 분리주 No. 1882-5로부터 용매추출, Amberlite XAD-4, silica, Lobar low pressure LC를 거쳐 항진균 활성물질 MT-1882-I과 K562 cell의 소포형성을 억제하는 활성물질 MT 1882-II를 분리하였다. 이 물질들에 대한 이화학적 성질의 조사와 UV, $^1H-NMR$, $^13C-NMR$, mass spectrum의 분석에 의하여 MT 1882-II은 piericidin $A_{1}$($C_{25}H_{37}0_4N$, MW 415), MT 1882-II는 glucopiericidin A($C_{31}H_{47}0_9N$, MW 577)로 동정하였다.

Keywords

References

  1. Elsevier Novel Microbial Products for Medicine and Agriculture Demain,L.A.;G.A.Somkuti;J.C.Hunter-Cevera;H.W.Rossmore
  2. Actinomycetes in Biotechnology Search and discovery of new antibiotics Okami,Y.;K.Hotta;M.Goodfellow;S.T.Williams;M.Mordarski(ed.)
  3. Inhibitors in Modern Biology and Medicine Hidaka,H.
  4. Biology of Actinomycetes '88 Proceedings of 7th International Symposium on Biology of Actinomycetes Isolation of immunomodulators from microbial sources Kohsaka,M.;T.Kino;H.Hatanaka;T.Goto;M.Okuhara;H.Aoki;H.Imanaka;Y.Okami;T.Beppu;H.Ogawara(ed.)
  5. Science v.24 Induction of differentiation in human promyelocytic leukemia cells by tumor promotors Rovera,G.;T.G.O'Brien;L.Diamond
  6. J. Cell. Physiol. v.138 Comparison of phorbol-12-myristate-13-acetate and dioctanoyl-sn-glycerol in the activation of EL4 thymoma cells. Stoeck,M.;R.Lees;G.Pantaleo;H.R.Mac-Donald
  7. Nippon Nogeikagaku Kaishi v.64 Chemical studies on natural products which modulate cell proliferation and differentiation Koshimizu,K.
  8. Science v.233 Studies and perspectives of protein Kinase C Nishizuka,Y.
  9. J. Biol. Chem. v.257 Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor promoting phorbolesters Castagna,M.;Y.Takai;K.Kaibuchi;K.Sano;U.Kikkawa;Y.Nishizuka
  10. Proc. Natl. Acad. Sci. U.S.A. v.80 Phorbol diester receptor copurifies with protein kinase C Niedel.J.E.;L.Kuhn;G.R.Bandenberk
  11. Blood v.45 Human chronic myelogenous cell line with positive Philadelphia chromosome Lozzio,C.B.;B.B.Lozzio
  12. Nature v.278 Induction of erythroid differntiation in the human leukemia cell line K562 Anderson,L.C.;M.Jokinen;G.C.Gahmberg
  13. Cancer Res. v.43 Tabilio,A.;G.P.Pelicci;G.Vinci;P.Mannoni;I.C.Civin;W.Vainchenker;U.Testa;M.Lipinski;H.Rochant;J.Breton-Gorius
  14. J. Antibiot v.41 Induction of morphological change of human myeloid leukemia by a novel antibiotic, tautomycin Magae,J.;C.Watanabe;H.Osada;X.C.Cheng;K.Isono
  15. 산업미생물학회지 v.19 Actinomycin계열 항생물질 MT-497을 생산하는 방선균 분리주 No.497의 동정 안종석;이영선;안순철;이정형;윤병대;민태익
  16. Agric. Biol. Chem v.27 Isolation and physiological activities of piericiden A. a nutural insecticide produced by streptomyces Tamura,S.;N.Takahashi;S.Miyamoto
  17. Agric. Biol. Chem v.41 Isolation and physical properties of new piericidins produced by Streptomyces pactum Yoshida,S.;K.Yoneyama;S.Shiraishi;A.Watanabe;N.Takahashi
  18. Nature v.308 The role of protein kinase C in cell surface signal transduction and tumor promotion Nishizuka,Y.
  19. J. Antibiot v.43 A new piericidin rhamnosid, 3'-rhamno piericidin $A_1$ Kimura,K.;S.Nakayama;N.Nakajima;M.Yoshihama;N.Miyata;G.Kawanishi
  20. J. Antibiot v.44 3'-Deoxytalopiericidin $A_1$, a novel analog of antitumor antibiotics from oligotroph Iwasaki,H.;K.Kamisango;H.Kuboniwa;H.Sasaki;S.Matsubara
  21. J. Antibiot v.40 New piericidin glucosides, glucopiericidin A and B Mstsumoto,M.;K.Mogi;K.Nagaoka;S.Ishizeki;R.Kawahara;T.Nakashima
  22. J. Antibiot v.42 Novel cytocidal antibiotics, glucopiericidinols $A_1$ and $A_2$Taxonomy, fermentation, isolation, structure eludidation and biological characteristics Funayama,S.;M.Ishibashi;Y.Anraku;M.Miyauchi;H.Mori;K.Komiyama;S.Omura
  23. J. Antibiot v.41 Rapid screening method for inhibitors of protein kinase C Osada,H.;J.Magae;C.Watanabe;K.Isono
  24. Biochem. Biophys. Res. Commun. v.135 Staurosporine, a potent inhibitor of phospholipid/$Ca^2-$ dependent protein kinase Tamaoki,T.;H.Nomoto;I.Takahashi;Y.Kato;M.Morimoto;F.Tomita
  25. J. Antibiot v.42 Calphostins(UCN-1028) novel and specific inhibitors of protein kinase C Kobayashi,E.;K.Ando;H.Nakano;T.Iida;H.Ohno;M.Morimoto;T.Tamaoki
  26. J. Biol. Chem. v.263 Sangivamycin, a nucleoside analogue is a potent inhibitor of protein kinase C Loomis,C.R.;R.M.Bell
  27. J. Antibiot v.44 Isolation and structure determination of a novel phosphatidyl inositol turnover inhibitor piericidin B1 N-oxide Nishioka,H.;T.Sawa;H.Naganawa;T.Takeuchi;K.Umezawa