Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Studies on the Structure and Biological Activity of Microcystins Produced from Korean Cyanobacteria, Microcystis Species

한국산 남조류 Microcystis로부터 생산된 microcystin 구조와 생물활성에 관한 연구

  • Choi, Byoung Wook (Department of Industrial Chemistry, Taejon Natl. Univ. of Technology) ;
  • Noh, Young Ho (Department of Industrial Chemistry, Taejon Natl. Univ. of Technology) ;
  • Lee, Jong-Soo (College of Fisheries, Gyeongsang Natl. Univ.)
  • 최병욱 (대전산업대학교 공업화학과) ;
  • 노영호 (대전산업대학교 공업화학과) ;
  • 이종수 (경상대학교 수산대학 수산가공과)
  • Received : 1997.03.06
  • Accepted : 1997.05.29
  • Published : 1997.08.10
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Abstract

Hepatotoxic cyanobacteria, Microcystis species, were collected from the Nakdong River and we could isolate hepatotoxins, microcystin-LR and microcystin-RR, which are also strong inhibitors of protein phosphatase 1 and 2A. From the microcystins, several microcystin derivatives were synthesized and tested on the mouse toxicity in order to establish the structure-activity relationship. Esterification od carboxyl groups of Glu and MeAsp residue produced nontoxic compounds. However, when we reduced the Mdha residue with sodium borohydride into Ala residue, toxicity was still maintained. Also, the change of guanidyl moiety of Arg residue in microcystin-LR into dimethylpyrimidyl moiety did not change the toxicity of microcystins as well. Thus the carboxyl groups seem to play important roles in binding with protein phosphatase 1 and 2A, whereas Mdha residue and the guanidyl moiety of Arg residue do not.

낙동강에서 채취한 남조류 Microcystis로부터 간독성물질이자 protein phosphatase 1과 2A의 강력한 억제제인 microcystin-LR과 microcystin-RR을 분리하였다. 이들 물질의 독성과 구조와의 관계들을 알아보기 위하여 몇가지 유도체들을 합성하여 독성실험을 하였다. Glu와 MeAsp의 카르복실기를 에스테르화할 경우 독성을 잃어버리는 것을 알 수 있었다. 반면에 Mdha 잔기의 이중결합을 $NaBH_4$로 환원하여 Ala잔기로 전환한 경우에는 독성을 그대로 유지하였고 또한 microcystin-LR의 Arg잔기의 guanidyl기를 dimethylpyrimidyl기로 변환한 경우에도 독성에는 크게 영향을 주지 않는 것을 알 수 있었다. 따라서 2개의 카르복실기는 microcystin이 독성을 나타내는데 아주 중요한 역할을 하는 반면에, Mdha 및 Arg잔기의 존재는 큰 역할을 하지 않는 것으로 여겨진다.

Keywords

Acknowledgement

Supported by : 한국학술진흥재단

References

  1. Medical Aspects of Phycology M. Schwimmer;D. Schwimmer;D. F. Jackson(ed)
  2. EPA/600R92/079 W. W. Carmichael;R. S. Saferman
  3. J. Kor. J. Limnol. v.22 K. S. Cho;B. C. Kim;W. M. Heo;S. Cho;S.
  4. Nature (London) v.18 G. Francis
  5. Advances in Botanical Research W. W. Carmichael;J. A. Callow(ed)
  6. Handbook of Natural Toxins W. W. Carmichael;A. T. Tu(ed)
  7. Can J. Physiol. v.37 C. T. Bishop;E. F. L. J. Anet;P. R. Gorham
  8. Toxicon v.20 D. W. Botes;H. Kruger;C. C. Viljoen
  9. Toxicon v.20 D. W. Botes;C. C. Vilojeon;H. Kruger;P. L. Wessels;D. H. Williams
  10. J. Chem. Soc., Chem. Commun. S. Santikarn;D. H. Willims;R. J. Smith;S. J. Hammond;D. W. Botes;A. Tuinman;P. L. Wessels;C. C. Viljeon;H. Kruger
  11. J. Chem. Soc., Perkin Trans D. P. Botes;A. A. Tuinman;P. L. Wessels;C. L. Viljoen;H. Krugh;D. H. Williams;S. Santrkarn;R. J. Smith;S. J. Hammond
  12. J. Chem. Soc., Perkin Trans D. P. Botes;P. L. Wessels;H. Krugh;M. T. C. Runneger;S. Santikarn;R. J. Smith;J. C. J. Barna;D. H. Williams
  13. J. Am. Chem. Soc. v.110 K. L. Rinehart;K.-I. Harada;M. Namikoshi;C. Chen;C. A. Harvis
  14. Tetrahedron Lett. v.28 T. Kusumi;T. Ooi;M. M. Watanabe
  15. J. Appl. Phycol. v.1 T. Ooi;T. Kusumi;H. Kakisawa;M. M. Watanabe
  16. J. chromatogr. v.408 P. S. Gathercole;P. G.
  17. Pro. Natl. Acad. Sci. USA v.86 T. Krishanamurthy;L. Szafraniec;D. F. Hunt;J. Shabanowitz;J. R. Yates Ⅲ;C. R. Hauer;W. W. Carmichael;O. Skulberg;G. F. Godd;S. Missler
  18. Toxicon v.27 R. D. Stoner;W. H. Adams;D. N. Slatkin;H. W. Siegelman
  19. Toxicon v.27 J. A. O. Meriluoto;A. Sandstroin;J. E. Eriksson;G. Remand;A. G. Craig;J. Chattopadhyaya
  20. Appl. Environ. Microbiol. v.55 K. Sivonen;W. W. Carmichael;A. M. Dahlem;K. L. Rinehant;J. Kivtranta;S. I. Niemela
  21. J. Org. Chem. v.55 M. Namikoshi;K. L. Rinehart;R. Sakai
  22. Chem. Res. Toxicol. v.3 K.-I. Harada;K. Ogawa;H. Murata;M. Suzuki
  23. Toxicon v.29 K.-I. Harada;K. Ogawa;K. Matsuura;H. Nagai;H. Murata;M. Suzuki;Y. Itezono;N. Nakayama;M. Shirai;M. Nakano
  24. Chem. Res. Toxicol. v.4 K.-I. Harada;K. Ogawa;Y. Kimura;H. Murata;M. Suzuki;P. M. Thorn;W. R. Evans;W. W. Carmichael
  25. J. Org. Chem. v.57 M. Namikoshi;K. L. Rinehart;R. Sakai;R. R. Stotts;A. M. Dahlem;V. R. Beasley;W. W. Carmichael;W. R. Evans
  26. Tetrahedron Lett. v.34 B. W. Choi;M. Namikoshi;F. Sun;K. L. Rinehart;W. W. Carmichael;A. M. Kaup;W. R. Evans;V. R. Beasley
  27. J. Appl. Phycol. v.6 K. L. Rinehart;M. Namikoshi;B. W. Choi
  28. J. Org. Chem. v.60 M. Namikoshi;F. Sun;B. W. Choi;K. L. Rinehart;W. W. Carmichael;W. R. Evans;V. R. Beasley
  29. J. Org. Chem. v.59 M. Namikoshi;B. W. Choi;R. Sakai;F. Sun;K. L. Rinehart
  30. Tetrahedron Lett. v.33 E. Dlip de Silva;D. E. Williams;R. J. Andersen;H. Klix;C. F. B. Holmes;T. M. Allen
  31. FEBS Lett. v.264 C. MacKintoshi;K. A. Beattie;S. Klumpp;P. Cohen;G. A. Codd
  32. Biochem. Biophys. Res. Commun. v.124 J. L. Witten;M. H. Schaffer;M. O'Shea;J. C. Cook;M. E. Hemling;K. L. Rinehart, Jr.
  33. Anal. Biochem. v.89 A. Mori;T. Ichimura;H. Matsumoto
  34. Ph.D. Thesis, University of Illinois at Urbana-Champaign B. W. Choi