Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Toward the Virtual Screening of α-Glucosidase Inhibitors with the Homology-Modeled Protein Structure

  • Park, Jung-Hum (Department of Bioscience and Biotechnology, Sejong University) ;
  • Ko, Sung-Min (Department of Bioscience and Biotechnology, Sejong University) ;
  • Park, Hwang-Seo (Department of Bioscience and Biotechnology, Sejong University)
  • Published : 2008.05.20
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Abstract

Discovery of $\alpha$-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate mediated diseases. As a method for the discovery of new novel inhibitors of $\alpha$-glucosidase, we have addressed the performance of the computer-aided drug design protocol involving the homology modeling of $\alpha$-glucosidase and the structure-based virtual screening with the two docking tools: FlexX and the automated and improved AutoDock implementing the effects of ligand solvation in the scoring function. The homology modeling of $\alpha$-glucosidase from baker’s yeast provides a high-quality 3-D structure enabling the structure-based inhibitor design. Of the two docking programs under consideration, AutoDock is found to be more accurate than FlexX in terms of scoring putative ligands to the extent of 5-fold enhancement of hit rate in database screening when 1% of database coverage is used as a cutoff. A detailed binding mode analysis of the known inhibitors shows that they can be stabilized in the active site of $\alpha$- glucosidase through the simultaneous establishment of the multiple hydrogen bond and hydrophobic interactions. The present study demonstrates the usefulness of the automated AutoDock program with the improved scoring function as a docking tool for virtual screening of new $\alpha$-glucosidase inhibitors as well as for binding mode analysis to elucidate the activities of known inhibitors.

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References

  1. Kimura, A.; Lee, J.-H.; Lee, I.-S.; Lee, H.-S.; Park, K.-H.; Chiba, S.; Kim, D. Carbohydr. Res. 2004, 339, 1035 https://doi.org/10.1016/j.carres.2003.10.035
  2. Heightman, T. D.; Andrea, T.; Vasella, A. T. Angew. Chem. Int. Ed. 1999, 38, 750 https://doi.org/10.1002/(SICI)1521-3773(19990315)38:6<750::AID-ANIE750>3.0.CO;2-6
  3. Robinson, K. M.; Begovic, M. E.; Rhinehart, B. L.; Heineke, E. W.; Ducep, J. B.; Kastner, P. R.; Marshall, F. N.; Danzin, C. Diabetes 1991, 40, 825 https://doi.org/10.2337/diabetes.40.7.825
  4. Braun, C.; Brayer, G. D.; Withers, S. G. J. Biol. Chem. 1995, 270, 26778 https://doi.org/10.1074/jbc.270.45.26778
  5. Dwek, R. A.; Butters, T. D.; Platt, F. M.; Nicole Zitzmann, N. Nature Rev. Drug. Discov. 2002, 1, 65 https://doi.org/10.1038/nrd708
  6. Humphries, M. J.; Matsumoto, K.; White, S. L.; Olden, K. Cancer Res. 1986, 46, 5215
  7. Mehta, A.; Zitzmann, N.; Rudd, P. M.; Block, T. M.; Dwek, R. A. FEBS Lett. 1998, 430, 17 https://doi.org/10.1016/S0014-5793(98)00525-0
  8. Karpas, A.; Fleet, G. W. J.; Dwek, R. A.; Petursson, S.; Namgoong, S. K.; Ramsden, N. G.; Jacob, G. S.; Rademacher, T. W. Proc. Natl. Acad. Sci. USA 1988, 85, 9229 https://doi.org/10.1073/pnas.85.23.9229
  9. Zitzmann, N.; Mehta, A. S.; Carrouee, S.; Butters, T. D.; Platt, F. M.; McCauley, J.; Blumberg, B. S.; Dwek, R. A.; Block, T. M. Proc. Natl. Acad. Sci. USA 1999, 96, 11878 https://doi.org/10.1073/pnas.96.21.11878
  10. Yee, H. S.; Fong, N. T. Pharmacotherapy 1996, 16, 792
  11. de Melo, E. B.; Gomes, A. S.; Carvalho, I. Tetrahedron 2006, 62, 10277 https://doi.org/10.1016/j.tet.2006.08.055
  12. Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515 https://doi.org/10.1021/cr000433k
  13. Xu, H.-W.; Dai, G.-F.; Liu, G.-Z.; Wang, J.-F.; Liu, H.-M. Bioorg. Med. Chem. 2007, 15, 4247 https://doi.org/10.1016/j.bmc.2007.03.063
  14. Tanabe, G.; Yoshikai, K.; Hatanaka, T.; Yamamoto, M.; Shao, Y.; Minematsu, T.; Muraoka, O.; Wang, T.; Matsuda, H.; Yoshikawa, M. Bioorg. Med. Chem. 2007, 15, 3926 https://doi.org/10.1016/j.bmc.2006.10.014
  15. Liu, Y.; Ma, L.; Chen, W.-H.; Wang, B.; Xu, Z.-L. Bioorg. Med. Chem. 2007, 15, 2810 https://doi.org/10.1016/j.bmc.2007.02.030
  16. Pandey, J.; Dwivedi, N.; Singh, N.; Srivastava, A. K.; Tamarkar, A.; Tripathi, R. P. Bioorg. Med. Chem. Lett. 2007, 17, 1321 https://doi.org/10.1016/j.bmcl.2006.12.002
  17. Hakamata, W.; Nakanishi, I.; Masuda, Y.; Shimizu, T.; Higuchi, H.; Nakamura, Y.; Saito, S.; Urano, S.; Oku, T.; Ozawa, T.; Ikota, N.; Miyata, N.; Okuda, H.; Fukuhara, K. J. Am. Chem. Soc. 2006, 128, 6524 https://doi.org/10.1021/ja057763c
  18. Dai, G.-F.; Xu, H.-W.; Wang, J.-F.; Liu, F.-W.; Liu, H.-M. Bioorg. Med. Chem. Lett. 2006, 16, 2710 https://doi.org/10.1016/j.bmcl.2006.02.011
  19. Liu, H.; Sim, L.; Rose, D. R.; Pinto, B. M. J. Org. Chem. 2006, 71, 3007 https://doi.org/10.1021/jo052539r
  20. Seo, W. D.; Kim, J. H.; Kang, J. E.; Ryu, H. W.; Curtis-Long, M. J.; Lee, H. S.; Yang, M. S.; Park, K. H. Bioorg. Med. Chem. Lett. 2005, 15, 5514 https://doi.org/10.1016/j.bmcl.2005.08.087
  21. Luo, J.-G.; Wang, X.-B.; Ma, L.; Kong, L.-Y. Bioorg. Med. Chem. Lett. 2007, 17, 4460 https://doi.org/10.1016/j.bmcl.2007.06.011
  22. Saludes, J. P.; Lievens, S. C.; Molinski, T. F. J. Nat. Prod. 2007, 70, 436 https://doi.org/10.1021/np060551o
  23. Du, Z.-Y.; Liu, R.-R.; Shao, W.-Y.; Mao, X. P.; Ma, L.; Gu, L.-Q.; Huang, Z.-S.; Chan, A. S. C. Eur. J. Med. Chem. 2006, 41, 213 https://doi.org/10.1016/j.ejmech.2005.10.012
  24. Lodge, J. A.; Maier, T.; Liebl, W.; Hoffmann, V.; Sträter, N. J. Biol. Chem. 2003, 278, 19151 https://doi.org/10.1074/jbc.M211626200
  25. Rajan, S. S.; Yang, X.; Collart, F.; Yip, V. L. Y.; Withers, S. G.; Varrot, A.; Thompson, J.; Davies, G. J.; Anderson, W. F. Structure 2004, 12, 1619 https://doi.org/10.1016/j.str.2004.06.020
  26. Zou, X.; Sun, Y.; Kuntz, I. D. J. Am. Chem. Soc. 1999, 121, 8033 https://doi.org/10.1021/ja984102p
  27. Shoichet, B. K.; Leach, A. R.; Kuntz, I. D. Proteins 1999, 34, 4 https://doi.org/10.1002/(SICI)1097-0134(19990101)34:1<4::AID-PROT2>3.0.CO;2-6
  28. Watanabe, K.; Hata, Y.; Kizaki, H.; Katsube, Y.; Suzuki, S. J. Mol. Biol. 1997, 269, 142 https://doi.org/10.1006/jmbi.1997.1018
  29. Bairoch, A.; Apweiler, R. Nucl. Acids Res. 1999, 27, 49 https://doi.org/10.1093/nar/27.1.49
  30. Thompson, J. D.; Higgins, D. G.; Gibson, T. J. Nucl. Acids Res. 1994, 22, 4673 https://doi.org/10.1093/nar/22.22.4673
  31. Sali, A.; Blundell, T. L. J. Mol. Biol. 1993, 234, 779 https://doi.org/10.1006/jmbi.1993.1626
  32. Fiser, A.; Do, R. K. G.; Sali, A. Protein Sci. 2000, 9, 1753 https://doi.org/10.1110/ps.9.9.1753
  33. Sippl, M. J. Proteins 1993, 17, 355 https://doi.org/10.1002/prot.340170404
  34. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Adv. Drug. Delivery. Rev. 1997, 23, 3 https://doi.org/10.1016/S0169-409X(96)00423-1
  35. Gasteiger, J.; Marsili, M. Tetrahedron 1980, 36, 3219 https://doi.org/10.1016/0040-4020(80)80168-2
  36. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. J. Comput. Chem. 1998, 19, 1639 https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
  37. Park, H.; Lee, J.; Lee, S. Proteins 2006, 65, 549 https://doi.org/10.1002/prot.21183
  38. Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University Press: Oxford, 1997
  39. Mehler, E. L.; Solmajer, T. Protein Eng. 1991, 4, 903 https://doi.org/10.1093/protein/4.8.903
  40. Stouten, P. F. W.; Frömmel, C.; Nakamura, H.; Sander, C. Mol. Simul. 1993, 10, 97 https://doi.org/10.1080/08927029308022161
  41. Kang, H.; Choi, H.; Park, H. J. Chem. Inf. Model. 2007, 47, 509 https://doi.org/10.1021/ci600453b
  42. Roujeinikova, A.; Raasch, C.; Sedelnikova, S.; Liebl, W.; Rice, D. W. J. Mol. Biol. 2002, 321, 149 https://doi.org/10.1016/S0022-2836(02)00570-3
  43. Bohm, H. J. J. Comput.-Aided Mol. Des. 1994, 8, 243 https://doi.org/10.1007/BF00126743
  44. Baker, D.; Sali, A. Science 2001, 294, 93 https://doi.org/10.1126/science.1065659
  45. Nishio, T.; Hakamata, W.; Kimura, A.; Chiba, S.; Takatsuki, A.; Kawachi, R.; Oku, T. Carbohydr. Res. 2002, 337, 629 https://doi.org/10.1016/S0008-6215(02)00026-5
  46. Zhou, J.-M.; Zhou, J.-H.; Meng, Y.; Chen, M.-B. J. Chem. Theory Comput. 2006, 2, 157 https://doi.org/10.1021/ct050168g

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