The design, synthesis, and biological evaluation of analogues of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: rational modifications imparting PP1 selectivity

Author:

Aggen James B,Humphrey John M,Gauss Carla-Maria,Huang Hsien-Bin,Nairn Angus C,Chamberlin A.Richard

Publisher

Elsevier BV

Subject

Organic Chemistry,Clinical Biochemistry,Drug Discovery,Pharmaceutical Science,Molecular Biology,Molecular Medicine,Biochemistry

Reference70 articles.

1. For a recent review on inhibitors of PP1/PP2A, see: (a) Sheppeck, J. E.; Gauss C.-M.; Chamberlin A. R. Bioorg. Med. Chem. 1997, 5, 1739. For recent examples of the use of natural product PP1/PP2A inhibitors to study the biological processess, see: (b) Sontag, E.; Sontag, J. M.; Garcia, A. EMBO J. 1997, 16, 5662. (c) Meisinger, J.; Patel, S.; Vellody, K.; Bergstrom, R.; Benefield, J.; Lozanzo, Y.; Young, M. R. I. Cancer Lett. 1997, 111, 87. (d) Brockdorff, J.; Nielsen, M.; Dobson, P.; Geisler, C.; Ropke, C.; Svedjgaard, A., Odum, N. Tissue Antigens 1997, 49, 228. (e) Favre, B.; Turowski, P.; Hemmings, B. A. J. Biol. Chem. 1997, 272, 13856. (f) Sansom, S. C.; Stockland, J. D.; Hall, D.; Williams, B. J. Biol. Chem. 1997, 272, 9902. (g) Hernandez, M. L.; Martinez, M. J.; Lopez de Heredia, M.; Ochoa, B. Biochim. Biophys. Acta 1997, 1349, 233.

2. For reviews on the roles of PP1 and PP2A in cellular processes, see: (a) Rusnak, F.; Yu, L. A.; Mertz, P. J. Biological Inorg. Chem. 1996, 1, 388. (b) Stark, M. J. R. Yeast 1996, 12, 1647. (c) Schonthol, A. H. Seminars in Cancer Biol. 1995, 6, 239. (d) Wera, S.; Hemmings, B. A. Biochem. J. 1995, 311, 17. (e) Shenolikar, S. Annu. Rev. Cell Biol. 1994, 10, 55.

3. Goldberg, J.; Huang, H. B.; Kwon, Y. G.; Greengard, P.; Nairn, A. C.; Kuriyan, J. Nature (London) 1995, 376, 745. The structure of a PP1/Tungstate complex was also reported: Egloff, M.-P.; Cohen, P. T. W.; Reinemer, P.; Barford, D. J. Mol. Biol. 1995, 254, 942.

4. For the preparation of our PP1/PP2A bound microcystin models, see: (a) Gauss, C. M.; Sheppeck, J. E.; Narin, A. C.; Chamberlin, A. R. Bioorg, Med. Chem. 1997, 5, 1751. For other recent modeling efforts in this area, see: (b) Lindvall, M. K.; Pihko, P. M.; Koskinen, A. M. P. J. Biol. Chem. 1997, 272, 23312. (c) Bagu, J. R.; Sykes, B. D.; Craig, M. M.; Holmes, C. F. B. J. Biol. Chem. 1997, 272, 5087. (d) Gupta, V.; Ogawa, A. K.; Du, X.; Houk, K. N.; Armstrong, R. W. J. Med. Chem. 1997, 40, 3199.

5. For site-directed mutagenesis studies on PP1/PP2A, see: (a) Huang, H.; Horiuchi, A.; Goldberg, J.; Greengard, P.; Narin, A. Proc. Natl. Acad. Sci. USA 1997, 94, 3530. (b) Zhang, Z.; Zhao, S.; Long, F.; Zhang, L.; Bait, G.; Shima, H.; Nagao, M.; Lee, E. Y. C. J. Biol. Chem. 1994, 269, 16997. (c) Runnegar, M.; Berndt, N.; Kong, S. M.; Lee, E. Y. C.; Zhang, L. Biochem. and Biophys. Res. Comm. 1995, 216, 162. Also, see ref [3].

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