Structural origin of selectivity in class II-selective histone deacetylase inhibitors

Journal of Medicinal Chemistry

Volumn 51, Issue 10, 2008, Pages 2898-2906

  Estiu, Guillermina ^a   Greenberg, Edward ^b   Harrison, Christopher B ^a   Kwiatkowski, Nicholas P ^b   Mazitschek, Ralph ^b   Bradner, James E ^b   Wiest, Olaf ^a  

^a UNIVERSITY OF NOTRE DAME   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC ACID; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE 8; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID; METHIONINE; NK 308; PHENYLALANINE; SULFUR; TUBACIN; VORINOSTAT;

ARTICLE; DRUG DESIGN; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; PROTEIN STRUCTURE; SIMULATION; STRUCTURE ACTIVITY RELATION;

ANILIDES; CRYSTALLOGRAPHY, X-RAY; HISTONE DEACETYLASES; HYDROXAMIC ACIDS; ISOENZYMES; MODELS, MOLECULAR; PROTEIN CONFORMATION; REPRESSOR PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 43949130430     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm7015254     Document Type: Article

References (73)

1. (a) Baylin, S. B.; Ohm, J. E. Epigenetic gene silencing in cancer: a mechanism for early oncogenic pathway addiction. Nature Rev. Cancer 2006, 6, 107-116.
2. (b) Xu, W. S.; Parmigiani, R. B.; Marks, P. A. Histone deacetylase inhibitors. Molecular mechanisms of action. Oncogene 2007, 26, 5541-5552.
3. Lund, A. H.; van Lohuizen, M. Epigenetics and cancer. Genes Dev. 2004, 18, 2315-2335.
4. Bolden, J.; Peart, M.; Johnstone, R. Anticancer activities of histone deacetylase inhibitors. Nature 2006, 5, 769-784.
5. (a) Roth, S. Y.; Denu, J. M.; Allis, C. D. Histone acetyltransferases. Annu. Rev. Biochem. 2001, 70, 81-120.
6. (b) Hodawadekar, S. C.; Marmorstein, R. Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene 2007, 26, 5528-5540.
7. Thiagallingam, S. Histone deacetylases: unique players in shaping the epigenetic histone code. Annu. NY Acad. Sci. 2003, 983, 84-100.
8. Rosato, R. R.; Grant, S. Histone deacetylase inhibitors in cancer therapy. Cancer Biol. Ther. 2003, 2, 30-37.
9. Villar-Garea, A.; Esteller, M. Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int. J. Cancer 2004, 112, 171-178.
10. Jabbour, E. J.; Giles, F. J. New agents in myelodysplastic syndromes. Curr. Hematol. Rep 2005, 4, 191-199.
11. Lindemann, R. K.; Gabrielli, B. Histone deacetylase inhibitors for the treatment of cancer. Johnstone, R. W. Cell Cycle 2004, 3, 779-788.
12. Marks, P.; Jiang, X. Histone deacetylese inhibitors in programmed cells death and cancer therapy. Cell Cycle 2005, 4, 549-551.
13. Gregoretti, I.; Lee, Y. -M.; Goodson, H. V. Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J. Mol. Biol. 2004, 338, 17-31.
14. (a) Bhalla, K. N. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J. Clin. Oncol. 2005, 23, 3971-3993.
15. (a) Haggarty, S. J.; Koeller, K. M.; Wong, J. C.; Grozinger, G. M.; Schreiber, S. L. Domain selective small molecule inhibitor of histone deacetylase 6 (HDAC6) mediated tubulin deacetylation. Proc. Natl. Acad. Sci. 2003, 100, 4389-4394.
16. (b) Hideshima, T.; Bradner, J. E.; Wong, J.; Chauhan, D.; Richardson, P.; Schreiber, S. L.; Anderson, K. C. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc. Natl. Acad. Sci. 2005, 102, 8567-8572.
17. (c) Santander, V. S.; Bisig, C. G.; Purro, S. A.; Casale, C. H.; Arce, C. A.; Barra, H. S. Tubulin must be acetylated in order to form a complex with membrane Na+,K+-ATPase and to inhibit its enzyme activity. Mol. Cell. Biochem. 2006, 91, 167-174.
18. (d) Cabrero, J. R.; Serrador, J. M.; Barreiro, O.; Mittelbrunn, M.; Naranjo-Suarez, S.; Martin-Cofreces, N.; Vicente-Manzanares, M.; Mazitschek, R.; Bradner, J. E.; Avila, J.; Valenzuela-Fernandez, A.; Sanchez-Madrid, F. Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of Its deacetylase activity. Mol. Biol. Cell 2006, 17, 3435-3445.
19. (e) Tran, A. D.; Marmo, T. P.; Salam, A. A.; Che, S.; Finkelstein, E.; Kabarriti, R.; Xenias, H. S.; Mazitschek, R.; Hubbert, C.; Kawaguchi, Y.; Sheetz, M. P.; Yao, T. P.; Bulinski, J. C. HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J. Cell Sci. 2007, 120, 1469-1479.
20. Hildmann, C.; Wegener, D.; Riester, D.; Hempel, R.; Schober, A.; Merana, J.; Giurato, L.; Guccione, S.; Nielsen, T. K.; Ficner, R.; Schwienhorst, A. Substrate an inhibitor specificity of class 1 and class 2 histone deacetylases. J. Biotechnol. 2006, 124, 258-270.
21. Park, J. H.; Jung, Y.; Kim, T.; Kim, S.; Jong, H.-S.; Lee, J. W.; Kim, D.-K.; Lee, J.-S.; Kim, N. K.; Kim, T.-Y.; Bang, Y.-J. Class 1 histone deacetylase-selective novel synthetic inhibitors potently inhibit human tumor proliferation. Clin. Cancer Res. 2004, 10, 5271-5281.
22. Furumai, R.; Komatsu, Y.; Nishino, N.; Khochbin, N.; Yoshida, M.; Horinouchi, S. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 87-92.
23. (a) Kawaguchi, Y.; Kovacs, J.; McLaurin, A.; Vance, J. M.; Ito, A.; Yao, T. P. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003, 115, 727-738.
24. (b) Yang, X.-J.; Gregoire, S. Class II Histone Deacetylases: from Sequence to Function, Regulation, and Clinical Implication. Mol. Cell. Biol. 2005, 25, 2873-2884.
25. (c) Boyault, C.; Sadoul, K.; Pabion, M.; Khochbin, S. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene 2007, 26, 5468-5476.
26. Barnes, D. W.; Koehler, A. N.; Bradner, J. E.; Mazitschek, R.; Schreiber, S. L. Small molecule printing using compounds and methods to identify compounds that interact with a biological macromolecule. Patent WO2008013569.
27. Wang, D.-F; Wiest, O.; Helquist, P. Zinc binding in HDAC inhibitors. A DFT study. J. Org. Chem. 2007, 72, 5446-5449.
28. (a) Vanommeslaeghe, K.; Van Alsenoy, C.; De Proft, F.; Martins, J. C.; Tourwé, D.; Geerlings, P. Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase. Org. Biomol. Chem. 2003, 1, 2951-2957.
29. (b) Vanommeslaeghe, K.; De Proft, F.; Loverix, S.; Tourwé, D.; Geerlings, P. DFT-based ranking of zinc-binding groups in histone deacetylase inhibitors. Bioorg. Med. Chem. 2005, 13, 3987-3992.
30. (c) Vanommeslaeghe, K.; Loverix, S.; Geerlings, P.; Tourwé, D. Ab initio study of the binding of trichostatin A (TSA) in the active site of histone deacetylase like Protein (HDLP). Bioorg. Med. Chem. 2005, 13, 6070-6082.
31. (a) Somoza, J. R.; Skene, R. J.; Katz, B. A.; Moi, C.; Ho, J. D.; Jennings, A. J.; Luong, C.; Arvai, A.; Buggy, J. J.; Chi, E.; Tang, J.; Sang, B. C.; Verner, E.; Wynands, R.; Leahy, E. M.; Dougan, D.; Snell, G.; Navre, M.; Knuth, M. W.; Swanson, R. V.; McRee, D.; Tari, L. W. Structural snapshots of Human HDAC8 provide Insights into Class I Histone Deacetylases. Structure 2004, 12, 1325-1334.
32. (b) Vannini, A.; Volpari, C.; Filocamo, G.; Caroli Casavola, E.; Brunetti, M.; Renzoni, D.; Chakravarty, P.; Paolini, C.; De Francesco, R.; Gallinari, P.; Steinckuhler, C.; Di Marco, S. Crystal structure of a eukariotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 15064-15069.
33. Compare also the structure of the histone deacetylase-like protein (HDLP): (c) Finnin, M. S.; Donigian, J. R.; Cohen, A.; Richon, V. M.; Rifkind, R. A.; Marks, P. A.; Breslow, R.; Pavletich, N. P. Structure of histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999, 401, 188-193.
34. (a) Nielsen, T. K.; Christian, H.; Dickmanns, A.; Schwienhorst, A.; Ficner, R. Crystal structure of a bacterial class 2 histone deacetylase homologue. J. Mol. Biol. 2005, 354, 107-120, Note that two structures of a human class IIa HDAC have been recently deposited in the PDB under pdb codes 2pqo and 2pqp.
35. (b) Schuetz, A., Min, J., Loppnau, P.; Weigelt, J.; Sundstrom, M.; Arrowsmith, C. H., Edwards, A. M.; Bochkarev, A.; Plotnikov, A. N. To be published.
36. (a) Wang, D.-F.; Wiest, O.; Helquist, P.; Lan-Hargest, H.-Y.; Wiech, N. L. Toward selective histone deacetylase inhibitor design. Homology modeling, docking studies and molecular dynamic simulations of human class I histone deacetylases. J. Med. Chem. 2004, 47, 3409-3417.
37. (b) Wang, D.-F.; Wiest, O.; Helquist, P.; Wiech, N. L. On the function of the 14 A long internal cavity of histone deacetylase-like protein: Implications for the design of histone deacetylase inhibitors. J. Med. Chem. 2005, 48, 6936-6947.
38. (a) Altschul, S. F.; Gish, W.; Miller, W.; Myers, E. W.; Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 1990, 215, 403-410.
39. (b) Altschul, S. F.; Madden, T. L.; Schäffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25, 3389-3402.
40. (c) Schäffer, A. A.; Aravind, L.; Madden, T. L.; Shavirin, S.; Spouge, J. L.; Wolf, Y. I.; Koonin, E. V.; Altschul, S. F. Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. Nucleic Acids Res. 2001, 29, 2994-3005.
41. (a) Fiser, A.; Do, R. K.; Sali, A. Modeling of loops in protein structures. Protein Sci. 2000, 9, 1753-1773.
42. (b) Marti-Renom, M. A.; Stuart, A.; Fiser, A.; Sánchez, R.; Melo, F.; Sali, A. Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 291-325.
43. (c) Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 1993, 234, 779-815.
44. (a) Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 1993, 26, 283-291.
45. (b) Morris, A. L.; MacArthur, M. W.; Hutchinson, E. G.; Thornton, J. M. Stereochemical quality of protein structure coordinates. Proteins 1992, 12, 345-364.
46. McLachlan, A. D. Rapid comparison of protein structures. Acta Crystallogr. 1982, A38, 871-873.
47. Jorgensen, W. L.; Madura, J.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for the simulation of liquid water. J. Chem. Phys. 1983, 79, 926-935.
48. Schafmeister, C.; Ross, W. S.; Romanovski, V. LEaP, University of California: San Francisco, 1995.
49. Cieplak, P.; Caldwell, J.; Kollman, P. A. Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation: Aqueous solution free energies of methanol and N-ethyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases. J. Comput. Chem. 2001, 22, 1048-1057.
50. (a) Wang, J.; Wang, W.; Kollman, P. A.; Case, D. A. Automatic atom type and bond type perception in molecular mechanical calculations. J. Mol. Graph. Mod. 2006, 25, 247-260.
51. (b) Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general AMBER force field. J. Comput. Chem. 2004, 25, 1157-1174.
52. (a) Bayly, C. A.; Cieplak, P.; Cornell, W. D.; Kollman, P. A. A well behaved elestrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. J. Phys. Chem. 1993, 97, 10269-10280.
53. (b) Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E.; Debolt, S.; Ferguson, D.; Seibel, G.; Kollman, P.A. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput. Phys. Commun. 1995, 91, 1-41.
54. (c) Fox, T.; Kollman, P. A. Application of RESP methodology in the parametrization of organic solvents. J. Phys. Chem. B 1998, 102, 8070-8079.
55. Case, D. A.; Darden, T. A.; Cheatham, T. E.; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Merz, K. M.; Wang, B.; Pearlman, D. A.; Crowley, M.; Brozell, S.; Tsui, V.; Gohlke, H.; Mongan, J.; Hornak, V.; Cui, G.; Beroza, P.; Schafmeister, C.; Caldwell, J. W.; Ross, W. S.; Kollman, P. A., AMBER 8; University of California: San Francisco, CA, 2004.
56. Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 1977, 23, 327-341.
57. (a) Berendsen, H. J. C.; Potsma, J. P. M.; van Gunsteren, W. F.; DiNola, A. D.; Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684-3690.
58. (b) van Gunsteren, W. F.; Berendsen, H. J. C. Algorithm for macromolecular dynamics and constraint dynamics. Mol. Phys. 1977, 34, 1311-1327.
59. (a) Essman, V.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A smooth particle-mesh-Ewald method. J. Chem. Phys. 1995, 103, 8577-8593.
60. (b) Petersen, L. G. Accuracy and efficiency of the particle-mesh-Ewald method. J. Chem. Phys. 1995, 103, 3668-3679.
61. Kapustin, G. V.; Fejer, G.; Gronlund, J. L.; McCafferty, D. G.; Seto, E.; Etzkorn, F. A. Phosphorus-based SAHA analogues as histone deacetylase inhibitors. Org. Lett. 2003, 5, 3053-3056.
62. Khan, N.; Jeffers, M.; Kumar, S.; Hackett, C.; Boldog, F.; Khramtsov, N.; Qian, X.; Mills, E.; Berghs, S. C.; Carey, N.; Finn, P. W.; Collins, L. S.; Tumber, A.; Ritchie, J. W.; Jensen, P. B.; Lichenstein, H. S.; Sehested, M. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem. J. 2008, 409, 581-589.
63. KrennHrubec, K.; Marshall, B. L.; Hedglin, M.; Verdin, E.; Ulrich, S. M. Design and evaluation of linkerless hydroxamates as selective HDAC8 inhibitors. Bioorg. Med. Chem. 2007, 17, 2874-2878.
64. (b) Waltregny, D.; De Levai, L.; Glenisson, W.; Ly Tran, S.; North, B. J.; Bellahcene, A.; Weidle, U.; Verdin, E.; Castronovo, V. Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues. Am. J. Pathol. 2004, 165, 553-564.
65. (c) Waltregny, D.; Glenisson, W.; Tran, S. L.; North, B. J.; Verdin, E.; Colige, A.; Castronovo, V. Histone deacetylase HDAC8 associates with smooth muscle {alpha}-actin and is essential for smooth muscle cell contractility. FASEB J. 2005, 19, 966-968.
66. (a) Pal, D.; Chakrabarti, P. Non-hydrogen bond interaction involving the methionine sulfur atom. J. Biomol. Struct. Dyn. 2001, 19, 115-128.
67. (b) Tatko, C.; Waters, M. Investigation of the nature of the π/methionine interaction in beta hairpin peptide model systems. Protein Sci. 2004, 13, 2515-2522.
68. (c) Ringer, A. L.; Senenko, A.; Sherill, C. D. Models of S/π interactions in protein structures: Comparison of the H2S-benzene complex with PDB data. Protein Sci. 2007, 16, 2216-2223.
69. Chakrabarti, P.; Samanta, U. CH/pi Interaction in the Packing of the Adenine Ring in Protein Structures. J. Mol. Biol. 1995, 251, 9-14.
70. Samanta, U.; Pal, D.; Chakrabarti, P. Environment of tryptophan side chains in proteins. Proteins 2000, 38, 288-300.
71. Weerasinghe, S. V. W.; Estiu, G.; Wiest, O.; Pflum, M. K. H., submitted for publication.
72. (a) Simonini, M. V.; Camargo, L. M.; Dong, E.; Maloku, E.; Veldic, M.; Costa, E.; Guidotti, A. From the Cover: The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 1587-1592.
73. (b) Hess-Stumpp, H.; Bracker, T. U.; Henderson, D.; Politz, O. MS-275, a potent orally available inhibitor of histone deacetylases - The development of an anticancer agent. Int. J. Biochem. Cell Biol. 2007, 39, 1388-1405.