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논문 상세정보

Camptothecin 유도체의 Human Topoisomerase I-DNA 복합체에 대한 Docking 연구

Docking Studies of Camptothecin Analogues into Human Topoisomerase I-DNA Complex

약학회지 = Yakhak hoeji v.53 no.4 , 2009년, pp.222 - 227  
Abstract

Human topoisomerase I (Topo I) plays a pivotal role in cell replication, transcription and repair and, therefore, is an important anti-cancer target. 20S-camptothecin (CPT) is a representative Topo I inhibitor. Compounds belonging to CPT family inhibit the religation step of Topo I-DNA by binding to the DNA cleavage site. Computational docking studies with Surflex-Dock were carried out to investigate the binding modes between Topo I-DNA binary complex structure and the ligand such as 20S-CPT and 9,10-substituted 20S-CPT analogues. The docking results demonstrated that most of the compounds with $IC_{50}$ value under $0.5{\mu}M$ intercalated exactly between the -1 and +1 DNA bases, deeply toward the cleavage site. The complex was stabilized by hydrogen-bonding and hydrophobic interactions with both the enzyme and the DNA. The compounds with $IC_{50}$ value above $0.5{\mu}M$ were poorly docked and did not intercalate. In addition, the docking results confirmed the overall correlation between the $IC_{50}$ values and docking scores, indicating the possible use of the modeling for the prediction of biological activity and design of potential inhibitors.

참고문헌 (28)

  1. Wang, J. C. : DNA topoisomerases. Annual Review of Biochemistry 65, 635 (1996) 
  2. Stewart, L., Redinbo, M. R., Qiu, X., Hol, W. G. and Champoux, J. J. : A model for the mechanism of human topoisomerase I. Science (New York, N.Y) 279, 1534 (1998) 
  3. Staker, B. L., Feese, M. D., Cushman, M., Pommier, Y., Zembower, D., Stewart, L. and Burgin, A. B. : Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J. Med. Chem. 48, 2336 (2005) 
  4. Champoux, J. J. : DNA topoisomerases: structure, function, and mechanism. Annual Review of Biochemistry 70, 369 (2001) 
  5. Pourquier, P., Pilon, A. A., Kohlhagen, G., Mazumder, A., Sharma, A. and Pommier, Y. : Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps. Importance of DNA end phosphorylation and camptothecin effects. The Journal of Biological Chemistry 272, 26441 (1997) 
  6. Pourquier, P., Ueng, L. M., Kohlhagen, G., Mazumder, A., Gupta, M., Kohn, K. W. and Pommier, Y. : Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I. The Journal of Biological Chemistry 272, 7792 (1997) 
  7. Lesher, D. T. T., Pommier, Y., Stewart, L. and Redinbo, M. R. : 8- Oxoguanine rearranges the active site of human topoisomerase I. Proc. Natl. Acad. Sci. U.S.A. 99, 12102 (2002) 
  8. Chreneik, J. E., Burgin, A. B., Pommier, Y., Stewart, L. and Redinbo, M. R. : Structural impact of the leukemia drug 1-beta-D-arabinofuranosyleytosine (Ara-C) on the covalent human topoisomerase I-DNA complex. J. Biol. Chem. 278, 12461 (2003) 
  9. Meng, L. H., Liao, Z. Y. and Pommier, Y. : Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy. Current Topics in Medicinal Chemistry 3, 305 (2003) 
  10. Pizzolato, J. F. and Saltz, L. B. : The camptothecins. Lancet 361, 2235 (2003) 
  11. Wall, M. E. and Wani, M. C. : Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Research 55, 753 (1995) 
  12. Li, T. K. and Liu, L. F. : Tumor cell death induced by topoisomerase-targeting drugs. Annual Review of Pharmacology and Toxicology 41, 53 (2001) 
  13. Sordet, O., Khan, Q. A., Kohn, K. W. and Pommier, Y. : Apoptosis induced by topoisomerase inhibitors. Current Medicinal Chemistry 3, 271 (2003) 
  14. Redinbo, M. R., Champoux, J. J. and Hol, W. G. J. : Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA. Biochemistry 39, 6832 (2000) 
  15. Pommier, Y., Pourquier, P., Fan, Y. and Strumberg, D. : Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochimica et Biophysica Acta 1400, 83 (1998) 
  16. Fan, Y., Weinstein, J. N., Kohn, K. W., Shi, L. M. and Pommier, Y. : Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex with camptothecin. J. Med. Chem. 41, 2216 (1998) 
  17. Kerrigan, J. E. and Pilch, D. S. : A structural model for the ternary cleavable complex formed between human topoisomerase I, DNA, and camptothecin. Biochemistry 40, 9792 (2001) 
  18. Staker, B. L., Hjerrild, K., Feese, M. D., Behnke, C. A., Burgin, A. B., Jr. and Stewart, L. : The mechanism of topoisomerase I poisoning by a camptothecin analog. Proceedings of the National Academy of Sciences of the United States of America 99, 15387 (2002) 
  19. Laco, G. S., Du, W., Kohlhagen, G., Sayer, J. M., Jerina, D. M., Burke, T. G., Curran, D. P. and Pommier, Y. : Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studies. Bioorganic & Medicinal Chemistry 12, 5225 (2004) 
  20. Redinbo, M. R., Stewart, L., Kuhn, P., Champoux, J. J. and Hol, W. G. J. : Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science 279, 1504 (1998) 
  21. Laco, G. S., Collins, J. R., Luke, B. T., Kroth, H., Sayer, J. M., Jerina, D. M. and Pommier, Y. : Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model. Biochemistry 41, 1428 (2002) 
  22. Thomas, C. J., Rahier, N. J. and Hecht, S. M. : Camptothecin: current perspectives. Bioorganic & Medicinal Chemistry 12, 1585 (2004) 
  23. Chrencik, J. E., Staker, B. L., Burgin, A. B., Pourquier, P., Pommier, Y., Stewart, L. and Redinbo, M. R. : Mechanisms of camptothecin resistance by human topoisomerase I mutations. J. Mol. Biol. 339, 773 (2004) 
  24. Krogh, B. O. and Shuman, S. : Catalytic mechanism of DNA topoisomerase IB. Mol. Cell 5, 1035 (2000) 
  25. Jain, A. N. : Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J. Me.d Chem. 46, 499 (2003) 
  26. Jain, A. N. : Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search. J. Comput. Aided Mol. Des. 21, 281 (2007) 
  27. Jones, G., Willett, P., Glen, R. C., Leach, A. R. and Taylor, R. : Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 267, 727 (1997) 
  28. Wall, M. E., Wani, M. C., Nicholas, A. W., Manikumar, G., Tele, C., Moore, L., Truesdale, A., Leitner, P. and Besterman, J. M. : Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs. J. Med. Chem. 36, 2689 (1993) 

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