Mechanism-based modulator discovery for sirtuin-catalyzed deacetylation reaction

Mini-Reviews in Medicinal Chemistry

Volumn 13, Issue 1, 2013, Pages 132-154

  Zheng, Weiping ^a  

^a JIANGSU UNIVERSITY   (China)

Author keywords

Activator; Inhibitor; Mechanism; Mechanism based; Protein deacetylase; Sirtuin

Indexed keywords

ISONICOTINAMIDE; NICOTINAMIDE; SIRTUIN; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 6;

ACETYLATION; ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; DEACETYLATION; DRUG SCREENING; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; HUMAN; KINETICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLASMODIUM FALCIPARUM;

EID: 84875033669     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955713804484703     Document Type: Article

References (217)

1. Kouzarides, T. Acetylation: a regulatory modification to rival phosphorylation? EMBO J., 2000, 19, 1176-9.
2. Roth, S.Y.; Denu, J.M.; Allis, C.D. Histone acetyltransferases. Annu. Rev. Biochem., 2001, 70, 81-120.
3. Marmorstein, R.; Roth, S.Y. Histone acetyltransferases: function, structure, and catalysis. Curr. Opin. Genet. Dev., 2001, 11, 155-61.
4. Schreiber, S.L.; Bernstein, B.E. Signaling network model of chromatin. Cell, 2002, 111, 771-8.
5. Yang, X.J. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res., 2004, 32, 959-76.
6. Blander, G.; Guarente, L. The Sir2 family of protein deacetylases. Annu. Rev. Biochem., 2004, 73, 417-35.
7. Glozak, M.A.; Sengupta, N.; Zhang, X.; Seto, E. Acetylation and deacetylation of non-histone proteins. Gene, 2005, 363, 15-23.
8. Denu, J.M. The Sir2 family of protein deacetylases. Curr. Opin. Chem. Biol., 2005, 9, 431-40.
9. Sauve, A.A.; Wolberger, C.; Schramm, V.L.; Boeke, J.D. The biochemistry of sirtuins. Annu. Rev. Biochem., 2006, 75, 435-65.
10. Yang, X.J.; Seto, E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene, 2007, 26, 5310-18.
11. Saunders, L.R.; Verdin, E. Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene, 2007, 26, 5489-5504.
12. Hodawadekar, S.C.; Marmorstein, R. Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene, 2007, 26, 5528-40.
13. Batta, K.; Das, C.; Gadad, S.; Shandilya, J.; Kundu, T.K. Reversible acetylation of non histone proteins: role in cellular function and disease. Subcell. Biochem., 2007, 41, 193-212.
14. Shahbazian, M.D.; Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem., 2007, 76, 75-100.
15. Berndsen, C.E.; Denu, J.M. Catalysis and substrate selection by histone/protein lysine acetyltransferases. Curr. Opin. Struct. Biol., 2008, 18, 682-9.
16. Yang, X.J.; Seto, E. The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat. Rev. Mol. Cell Biol., 2008, 9, 206-18.
17. Arif, M.; Selvi, B.R.; Kundu, T.K. Lysine acetylation: the tale of a modification from transcription regulation to metabolism. Chembiochem, 2010, 11, 1501-4.
18. Arif, M.; Senapati, P.; Shandilya, J.; Kundu, T.K. Protein lysine acetylation in cellular function and its role in cancer manifestation. Biochim. Biophys. Acta, 2010, 1799, 702-16.
19. Huang, J.Y.; Hirschey, M.D.; Shimazu, T.; Ho, L.; Verdin, E. Mitochondrial sirtuins. Biochim. Biophys. Acta, 2010, 1804, 1645-51.
20. Aka, J.A.; Kim, G.W.; Yang, X.J. K-acetylation and its enzymes: overview and new developments. Handb. Exp. Pharmacol., 2011, (206), 1-12.
21. Kim, G.W.; Yang, X.J. Comprehensive lysine acetylomes emerging from bacteria to humans. Trends Biochem. Sci., 2011, 36, 211-20.
22. Yao, Y.L.; Yang, W.M. Beyond histone and deacetylase: an overview of cytoplasmic histone deacetylases and their nonhistone substrates. J. Biomed. Biotechnol., 2011, 2011, 146493.
23. Cen, Y.; Youn, D.Y.; Sauve, A.A. Advances in characterization of human sirtuin isoforms: chemistries, targets and therapeutic applications. Curr. Med. Chem., 2011, 18, 1919-35.
24. Mujtaba, S.; Zeng, L.; Zhou, M.M. Structure and acetyl-lysine recognition of the bromodomain. Oncogene, 2007, 26, 5521-27.
25. Sanchez, R.; Zhou, M.M. The role of human bromodomains in chromatin biology and gene transcription. Curr. Opin. Drug Discov. Devel., 2009, 12, 659-65.
26. +-dependent deacetylation reactions. Biochemistry, 2001, 40, 15456-63.
27. Pérez-Martín, J.; Uría, J.A.; Johnson, A.D. Phenotypic switching in Candida albicans is controlled by a SIR2 gene. EMBO J., 1999, 18, 2580-92.
28. Frye, R.A. Phylogenetic Classification of Prokaryotic and Eukaryotic Sir2-like Proteins. Biochem. Biophys. Res. Commun., 2000, 273, 793-8.
29. Trojer, P.; Brandtner, E.M.; Brosch, G.; Loidl, P.; Galehr, J.; Linzmaier, R.; Haas, H.; Mair, K.; Tribus, M.; Graessle, S. Histone deacetylases in fungi: novel members, new facts. Nucleic Acids Res., 2003, 31, 3971-81.
30. García-Salcedo, J.A.; Gijón, P.; Nolan, D.P.; Tebabi, P.; Pays, E. A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei. EMBO J., 2003, 22, 5851-62.
31. Thiagalingam, S.; Cheng, K.H.; Lee, H.J.; Mineva, N.; Thiagalingam, A.; Ponte, J.F. Histone deacetylases: unique players in shaping the epigenetic histone code. Ann. N. Y. Acad. Sci., 2003, 983, 84-100.
32. Gregoretti, I.V.; 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.
33. Figueiredo, L.; Scherf, A. Plasmodium telomeres and telomerase: the usual actors in an unusual scenario. Chromosome Res., 2005, 13, 517-24.
34. Domergue, R.; Castaño, I.; De Las Peñas, A.; Zupancic, M.; Lockatell, V.; Hebel, J.R.; Johnson, D.; Cormack, B.P. Nicotinic Acid Limitation Regulates Silencing of Candida Adhesins During UTI. Science, 2005, 308, 866-70.
35. Sereno, D.; Vergnes, B.; Mathieu-Daude, F.; Cordeiro da Silva, A.; Ouaissi, A. Looking for putative functions of the Leishmania cytosolic SIR2 deacetylase. Parasitol. Res., 2006, 100, 1-9.
36. Greiss, S.; Gartner, A. Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation. Mol. Cells, 2009, 28, 407-15.
37. Gu, J.; Deng, J.Y.; Li, R.; Wei, H.; Zhang, Z.; Zhou, Y.; Zhang, Y.; Zhang, X.E. Cloning and characterization of NAD-dependent protein deacetylase (Rv1151c) from Mycobacterium tuberculosis. Biochemistry (Mosc), 2009, 74, 743-8.
38. Dam, S.; Lohia, A. Entamoeba histolytica sirtuin EhSir2a deacetylates tubulin and regulates the number of microtubular assemblies during the cell cycle. Cell. Microbiol., 2010, 12, 1002-14.
39. Yasukawa, H.; Yagita, K. Silent information regulator 2 proteins encoded by Cryptosporidium parasites. Parasitol. Res., 2010, 107, 707-12.
40. Tucker, A.C.; Escalante-Semerena, J.C. Biologically active isoforms of CobB sirtuin deacetylase in Salmonella enterica and Erwinia amylovora. J. Bacteriol., 2010, 192, 6200-08.
41. +-dependent deacetylase. Parasitology, 2011, 138, 1245-58.
42. Li, Z.; Wen, J.; Lin, Y.; Wang, S.; Xue, P.; Zhang, Z.; Zhou, Y.; Wang, X.; Sui, L.; Bi, L.J.; Zhang, X.E. A Sir2-like protein participates in mycobacterial NHEJ. PLoS One, 2011, 6, e20045.
43. Michishita, E.; Park, J.Y.; Burneskis, J.M.; Barrett, J.C.; Horikawa, I. Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins. Mol. Biol. Cell, 2005, 16, 4623-35.
44. +-dependent histone deacetylase SIRT1. J. Biol. Chem., 2007, 282, 6823-32.
45. Starai, V.J.; Celic, I.; Cole, R.N.; Boeke, J.D.; Escalante-Semerena, J.C. Sir2-Dependent Activation of Acetyl-CoA Synthetase by Deacetylation of Active Lysine. Science, 2002, 298, 2390-2.
46. Li, R.; Gu, J.; Chen, Y.Y.; Xiao, C.L.; Wang, L.W.; Zhang, Z.P.; Bi, L.J.; Wei, H.P.; Wang, X.D.; Deng, J.Y.; Zhang, X.E. CobB regulates Escherichia coli chemotaxis by deacetylating the response regulator CheY. Mol. Microbiol., 2010, 76, 1162-74.
47. Xu, H.; Hegde, S.S.; Blanchard, J.S. Reversible acetylation and inactivation of Mycobacterium tuberculosis acetyl-CoA synthetase is dependent on cAMP. Biochemistry, 2011, 50, 5883-92.
48. Goyal, M.; Alam, A.; Iqbal, M.S.; Dey, S.; Bindu, S.; Pal, C.; Banerjee, A.; Chakrabarti, S.; Bandyopadhyay, U. Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum. Nucleic Acids Res., 2012, 40, 1174-90.
49. Smith, B.C.; Hallows, W.C.; Denu, J.M. Mechanisms and Molecular Probes of Sirtuins. Chem. Biol., 2008, 15, 1002-13.
50. Vaziri, H.; Dessain, S.K.; Ng Eaton, E.; Imai, S.I.; Frye, R.A.; Pandita, T.K.; Guarente, L.; Weinberg, R.A. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell, 2001, 107, 149-59.
51. Smith, J.S.; Avalos, J.; Celic, I.; Muhammad, S.; Wolberger, C.; Boeke, J.D. SIR2 family of NAD(+)-dependent protein deacetylases. Methods Enzymol., 2002, 353, 282-300.
52. Brunet, A.; Sweeney, L.B.; Sturgill, J.F.; Chua, K.F.; Greer, P.L.; Lin, Y.; Tran, H.; Ross, S.E.; Mostoslavsky, R.; Cohen, H.Y.; Hu, L.S.; Cheng, H.L.; Jedrychowski, M.P.; Gygi, S.P.; Sinclair, D.A.; Alt, F.W.; Greenberg, M.E. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 2004, 303, 2011-5.
53. Bereshchenko, O.R.; Gu, W.; Dalla-Favera, R. Acetylation inactivates the transcriptional repressor BCL6. Nat. Genet., 2002, 32, 606-13.
54. Yeung, F.; Hoberg, J.E.; Ramsey, C.S.; Keller, M.D.; Jones, D.R.; Frye, R.A.; Mayo, M.W. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J., 2004, 23, 2369-80.
55. Sartorelli, V.; Puri, P.L.; Hamamori, Y.; Ogryzko, V.; Chung, G.; Nakatani, Y.; Wang, J.Y.; Kedes, L. Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol. Cell, 1999, 4, 725-34.
56. Polesskaya, A.; Duquet, A.; Naguibneva, I.; Weise, C.; Vervisch, A.; Bengal, E.; Hucho, F.; Robin, P.; Harel-Bellan, A. CREBbinding protein/p300 activates MyoD by acetylation. J. Biol. Chem., 2000, 275, 34359-64.
57. Cohen, H.Y.; Lavu, S.; Bitterman, K.J.; Hekking, B.; Imahiyerobo, T.A.; Miller, C.; Frye, R.; Ploegh, H.; Kessler, B.M.; Sinclair, D.A. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol. Cell, 2004, 13, 627-38.
58. Jeong, J.; Juhn, K.; Lee, H.; Kim, S.H.; Min, B.H.; Lee, K.M.; Cho, M.H.; Park, G.H.; Lee, K.H. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp. Mol. Med., 2007, 39, 8-13.
59. Yamamori, T.; DeRicco, J.; Naqvi, A.; Hoffman, T.A.; Mattagajasingh, I.; Kasuno, K.; Jung, S.B.; Kim, C.S.; Irani, K. SIRT1 deacetylates APE1 and regulates cellular base excision repair. Nucleic Acids Res., 2010, 38, 832-45.
60. Fan, W.; Luo, J. SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Mol. Cell, 2010, 39, 247-58.
61. Kang, T.H.; Reardon, J.T.; Sancar, A. Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein. Nucleic Acids Res., 2011, 39, 3176-87.
62. Pagans, S.; Pedal, A.; North, B.J.; Kaehlcke, K.; Marshall, B.L.; Dorr, A.; Hetzer-Egger, C.; Henklein, P.; Frye, R.; McBurney, M.W.; Hruby, H.; Jung, M.; Verdin, E.; Ott, M. SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol., 2005, 3, e41.
63. Hirschey, M.D.; Shimazu, T.; Capra, J.A.; Pollard, K.S.; Verdin, E. SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2. Aging (Albany NY) 2011, 3, 635-42.
64. Hallows, W.C.; Yu, W.; Denu, J.M. Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1-mediated deacetylation. J. Biol. Chem., 2012, 287, 3850-8.
65. Zhang, Y.; Zhang, M.; Dong, H.; Yong, S.; Li, X.; Olashaw, N.; Kruk, P.A.; Cheng, J.Q.; Bai, W.; Chen, J.; Nicosia, S.V.; Zhang, X. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene, 2009, 28, 445-60.
66. Yamagata, K.; Kitabayashi, I. Sirt1 physically interacts with Tip60 and negatively regulates Tip60-mediated acetylation of H2AX. Biochem. Biophys. Res. Commun., 2009, 390, 1355-60.
67. Wang, J.; Chen, J. SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60. J. Biol. Chem., 2010, 285, 11458-64.
68. Peng, L.; Ling, H.; Yuan, Z.; Fang, B.; Bloom, G.; Fukasawa, K.; Koomen, J.; Chen, J.; Lane, W.S.; Seto, E. SIRT1 Negatively Regulates the Activities, Functions, and Protein Levels of hMOF and TIP60. Mol. Cell. Biol., 2012 May 14. [Epub ahead of print]
69. Peng, L.; Yuan, Z.; Ling, H.; Fukasawa, K.; Robertson, K.; Olashaw, N.; Koomen, J.; Chen, J.; Lane, W.S.; Seto, E. SIRT1 Deacetylates the DNA Methyltransferase 1 (DNMT1) Protein and Alters its Activities. Mol. Cell. Biol., 2011, 31, 4720-34.
70. Schwer, B.; Bunkenborg, J.; Verdin, R.O.; Andersen, J.S.; Verdin, E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc. Natl. Acad. Sci. USA, 2006, 103, 10224-9.
71. Hallows, W.C.; Lee, S.; Denu, J.M. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl. Acad. Sci. USA, 2006, 103, 10230-5.
72. Shimazu, T.; Hirschey, M.D.; Hua, L.; Dittenhafer-Reed, K.E.; Schwer, B.; Lombard, D.B.; Li, Y.; Bunkenborg, J.; Alt, F.W.; Denu, J.M.; Jacobson, M.P.; Verdin, E. SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab., 2010, 12, 654-61.
73. Ahn, B.H.; Kim, H.S.; Song, S.; Lee, I.H.; Liu, J.; Vassilopoulos, A.; Deng, C.X.; Finkel, T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl. Acad. Sci. USA, 2008, 105, 14447-52.
74. Cimen, H.; Han, M.J.; Yang, Y.; Tong, Q.; Koc, H.; Koc, E.C. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry, 2010, 49, 304-11.
75. Finley, L.W.; Haas, W.; Desquiret-Dumas, V.; Wallace, D.C.; Procaccio, V.; Gygi, S.P.; Haigis, M.C. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS One, 2011, 6, e23295.
76. Lu, Z.; Bourdi, M.; Li, J.H.; Aponte, A.M.; Chen, Y.; Lombard, D.B.; Gucek, M.; Pohl, L.R.; Sack, M.N. SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity. EMBO Rep., 2011, 12, 840-6.
77. Lombard, D.B.; Alt, F.W.; Cheng, H.L.; Bunkenborg, J.; Streeper, R.S.; Mostoslavsky, R.; Kim, J.; Yancopoulos, G.; Valenzuela, D.; Murphy, A.; Yang, Y.; Chen, Y.; Hirschey, M.D.; Bronson, R.T.; Haigis, M.; Guarente, L.P.; Farese, R.V. Jr.; Weissman, S.; Verdin, E.; Schwer, B. Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation. Mol. Cell. Biol., 2007, 27, 8807-14.
78. Schlicker, C.; Gertz, M.; Papatheodorou, P.; Kachholz, B.; Becker, C.F.W.; Steegborn, C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol., 2008, 382, 790-801.
79. Hallows, W.C.; Yu, W.; Smith, B.C.; Devries, M.K.; Ellinger, J.J.; Someya, S.; Shortreed, M.R.; Prolla, T.; Markley, J.L.; Smith, L.M.; Zhao, S.; Guan, K.L.; Denu, J.M. Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol. Cell, 2011, 41, 139-49.
80. Hirschey, M.D.; Shimazu, T.; Goetzman, E.; Jing, E.; Schwer, B.; Lombard, D.B.; Grueter, C.A.; Harris, C.; Biddinger, S.; Ilkayeva, O.R.; Stevens, R.D.; Li, Y.; Saha, A.K.; Ruderman, N.B.; Bain, J.R.; Newgard, C.B.; Farese, R.V. Jr.; Alt, F.W.; Kahn, C.R.; Verdin, E. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 2010, 464, 121-5.
81. Pillai, V.B.; Sundaresan, N.R.; Kim, G.; Gupta, M.; Rajamohan, S.B.; Pillai, J.B.; Samant, S.; Ravindra, P.V.; Isbatan, A.; Gupta, M.P. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J. Biol. Chem., 2010, 285, 3133-44.
82. Someya, S.; Yu, W.; Hallows, W.C.; Xu, J.; Vann, J.M.; Leeuwenburgh, C.; Tanokura, M.; Denu, J.M.; Prolla, T.A. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell, 2010, 143, 802-12.
83. Yu, W.; Dittenhafer-Reed, K.E.; Denu, J.M. SIRT3 Protein Deacetylates Isocitrate Dehydrogenase 2 (IDH2) and Regulates Mitochondrial Redox Status. J. Biol. Chem., 2012, 287, 14078-86.
84. Tao, R.; Coleman, M.C.; Pennington, J.D.; Ozden, O.; Park, S.H.; Jiang, H.; Kim, H.S.; Flynn, C.R.; Hill, S.; Hayes McDonald, W.; Olivier, A.K.; Spitz, D.R.; Gius, D. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol. Cell, 2010, 40, 893-904.
85. Qiu, X.; Brown, K.; Hirschey, M.D.; Verdin, E.; Chen, D. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab., 2010, 12, 662-7.
86. Chen, Y.; Zhang, J.; Lin, Y.; Lei, Q.; Guan, K.L.; Zhao, S.; Xiong, Y. Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep., 2011, 12, 534-41.
87. +-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. J. Biol. Chem., 2010, 285, 7417-29.
88. Shulga, N.; Wilson-Smith, R.; Pastorino, J.G. Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. J. Cell Sci., 2010, 123, 894-902.
89. Hafner, A.V.; Dai, J.; Gomes, A.P.; Xiao, C.Y.; Palmeira, C.M.; Rosenzweig, A.; Sinclair, D.A. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses agerelated cardiac hypertrophy. Aging (Albany NY) 2010, 2, 914-23.
90. +-dependent tubulin deacetylase. Mol. Cell, 2003, 11, 437-44.
91. Vaquero, A.; Scher, M.B.; Lee, D.H.; Sutton, A.; Cheng, H.L.; Alt, F.W.; Serrano, L.; Sternglanz, R.; Reinberg, D. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev., 2006, 20, 1256-61.
92. +-dependent deacetylation of H4 lysine 16 by class III HDACs. Oncogene, 2007, 26, 5505-20.
93. Jiang, W.; Wang, S.; Xiao, M.; Lin, Y.; Zhou, L.; Lei, Q.; Xiong, Y.; Guan, K.L.; Zhao, S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol. Cell, 2011, 43, 33-44.
94. Zuo, Q.; Wu, W.; Li, X.; Zhao, L.; Chen, W. HDAC6 and SIRT2 promote bladder cancer cell migration and invasion by targeting cortactin. Oncol. Rep., 2012, 27, 819-24.
95. Ma, L.; Gao, J.S.; Guan, Y.; Shi, X.; Zhang, H.; Ayrapetov, M.K.; Zhang, Z.; Xu, L.; Hyun, Y.M.; Kim, M.; Zhuang, S.; Chin, Y.E. Acetylation modulates prolactin receptor dimerization. Proc. Natl. Acad. Sci. USA, 2010, 107, 19314-9.
96. Jin, Y.H.; Kim, Y.J.; Kim, D.W.; Baek, K.H.; Kang, B.Y.; Yeo, C.Y.; Lee, K.Y. Sirt2 interacts with 14-3-3 beta/gamma and downregulates the activity of p53. Biochem. Biophys. Res. Commun., 2008, 368, 690-5.
97. Peck, B.; Chen, C.Y.; Ho, K.K.; Di Fruscia, P.; Myatt, S.S.; Coombes, R.C.; Fuchter, M.J.; Hsiao, C.D.; Lam, E.W. SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol. Cancer Ther., 2010, 9, 844-55.
98. Wang, F.; Nguyen, M.; Qin, F.X.; Tong, Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell, 2007, 6, 505-14.
99. Rothgiesser, K.M.; Erener, S.; Waibel, S.; Lüscher, B.; Hottiger, M.O. SIRT2 regulates NF-αB dependent gene expression through deacetylation of p65 Lys310. J. Cell Sci., 2010, 123, 4251-8.
100. Kim, H.S.; Vassilopoulos, A.; Wang, R.H.; Lahusen, T.; Xiao, Z.; Xu, X.; Li, C.; Veenstra, T.D.; Li, B.; Yu, H.; Ji, J.; Wang, X.W.; Park, S.H.; Cha, Y.I.; Gius, D.; Deng, C.X. SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. Cancer Cell, 2011, 20, 487-99.
101. Nakagawa, T.; Lomb, D.J.; Haigis, M.C.; Guarente, L. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell, 2009, 137, 560-70.
102. Michishita, E.; McCord, R.A.; Berber, E.; Kioi, M.; Padilla-Nash, H.; Damian, M.; Cheung, P.; Kusumoto, R.; Kawahara, T.L.A.; Barrett, J.C.; Chang, H.Y.; Bohr, V.A.; Ried, T.; Gozani, O.; Chua, K.F. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature, 2008, 452, 492-6.
103. Yang, B.; Zwaans, B.M.; Eckersdorff, M.; Lombard, D.B. The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle, 2009, 8, 2662-3.
104. Michishita, E.; McCord, R.A.; Boxer, L.D.; Barber, M.F.; Hong, T.; Gozani, O.; Chua, K.F. Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle, 2009, 8, 2664-6.
105. Kaidi, A.; Weinert, B.T.; Choudhary, C.; Jackson, S.P. Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science, 2010, 329, 1348-53.
106. Vakhrusheva, O.; Smolka, C.; Gajawada, P.; Kostin, S.; Boettger, T.; Kubin, T.; Braun, T.; Bober, E. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ. Res., 2008, 102, 703-10.
107. Peng, C.; Lu, Z.; Xie, Z.; Cheng, Z.; Chen, Y.; Tan, M.; Luo, H.; Zhang, Y.; He, W.; Yang, K.; Zwaans, B.M.; Tishkoff, D.; Ho, L.; Lombard, D.; He, T.C.; Dai, J.; Verdin, E.; Ye, Y.; Zhao, Y. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics, 2011, 10, M111.012658.
108. Du, J.; Zhou, Y.; Su, X.; Yu, J.J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Kim, J.H.; Choi, B.H.; He, B.; Chen, W.; Zhang, S.; Cerione, R.A.; Auwerx, J.; Hao, Q.; Lin, H. Sirt5 is a NADdependent protein lysine demalonylase and desuccinylase. Science, 2011, 334, 806-9.
109. Haigis, M.C.; Mostoslavsky, R.; Haigis, K.M.; Fahie, K.; Christodoulou, D.C.; Murphy, A.J.; Valenzuela, D.M.; Yancopoulos, G.D.; Karow, M.; Blander, G.; Wolberger, C.; Prolla, T.A.; Weindruch, R.; Alt, F.W.; Guarente, L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell, 2006, 126, 941-54.
110. Liszt, G.; Ford, E.; Kurtev, M.; Guarente, L. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J. Biol. Chem., 2005, 280, 21313-20.
111. Mao, Z.; Hine, C.; Tian, X.; Van Meter, M.; Au, M.; Vaidya, A.; Seluanov, A.; Gorbunova, V. SIRT6 promotes DNA repair under stress by activating PARP1. Science, 2011, 332, 1443-6.
112. Zhang, T.; Kraus, W.L. SIRT1-dependent regulation of chromatin and transcription: linking NAD(+) metabolism and signaling to the control of cellular functions. Biochim. Biophys. Acta, 2010, 1804, 1666-75.
113. Finkel, T.; Deng, C.X.; Mostoslavsky, R. Recent progress in the biology and physiology of sirtuins. Nature, 2009, 460, 587-91.
114. Liu, T.; Liu, P.Y.; Marshall, G.M. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res., 2009, 69, 1702-5.
115. Imai, S.; Guarente, L. Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol. Sci., 2010, 31, 212-20.
116. Yu, J.; Auwerx, J. Protein deacetylation by SIRT1: an emerging key post-translational modification in metabolic regulation. Pharmacol. Res., 2010, 62, 35-41.
117. Haigis, M.C.; Sinclair, D.A. Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol., 2010, 5, 253-95.
118. Verdin, E.; Hirschey, M.D.; Finley, L.W.; Haigis, M.C. Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem. Sci., 2010, 35, 669-75.
119. Zhang, H.S.; Wu, M.R. SIRT1 regulates Tat-induced HIV-1 transactivation through activating AMP-activated protein kinase. Virus Res., 2009, 146, 51-7.
120. Zhang, H.S.; Sang, W.W.; Wang, Y.O.; Liu, W. Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat-mediated long terminal repeat transactivation. J. Cell. Biochem., 2010, 110, 1464-70.
121. Knight, J.R.; Milner, J. SIRT1, metabolism and cancer. Curr. Opin. Oncol., 2012, 24, 68-75.
122. Li, X.; Kazgan, N. Mammalian sirtuins and energy metabolism. Int. J. Biol. Sci., 2011, 7, 575-87.
123. Horio, Y.; Hayashi, T.; Kuno, A.; Kunimoto, R. Cellular and molecular effects of sirtuins in health and disease. Clin. Sci. (Lond), 2011, 121, 191-203.
124. Bonda, D.J.; Lee, H.G.; Camins, A.; Pallàs, M.; Casadesus, G.; Smith, M.A.; Zhu, X. The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations. Lancet Neurol., 2011, 10, 275-9.
125. Schug, T.T.; Li, X. Sirtuin 1 in lipid metabolism and obesity. Ann. Med., 2011, 43, 198-211.
126. Guan, K.L.; Xiong, Y. Regulation of intermediary metabolism by protein acetylation. Trends Biochem. Sci., 2011, 36, 108-16.
127. Hirschey, M.D.; Shimazu, T.; Huang, J.Y.; Schwer, B.; Verdin, E. SIRT3 Regulates Mitochondrial Protein Acetylation and Intermediary Metabolism. Cold Spring Harb. Symp. Quant. Biol., 2011, 76, 267-77.
128. Zhong, L.; Mostoslavsky, R. Fine tuning our cellular factories: sirtuins in mitochondrial biology. Cell Metab., 2011, 13, 621-6.
129. Guarente, L. Sirtuins, Aging, and Metabolism. Cold Spring Harb. Symp. Quant. Biol., 2011, 76, 81-90.
130. Elliott, P.J.; Jirousek, M. Sirtuins: novel targets for metabolic disease. Curr. Opin. Investig. Drugs, 2008, 9, 371-8.
131. Outeiro, T.F.; Marques, O.; Kazantsev, A. Therapeutic role of sirtuins in neurodegenerative disease. Biochim. Biophys. Acta, 2008, 1782, 363-9.
132. Milne, J.C.; Denu, J.M. The Sirtuin family: therapeutic targets to treat diseases of aging. Curr. Opin. Chem. Biol., 2008, 12, 11-7.
133. +dependent histone deacetylases (sirtuins). Curr. Pharm. Des., 2008, 14, 562-73.
134. Cole, P.A. Chemical probes for histone-modifying enzymes. Nat. Chem. Biol., 2008, 4, 590-7.
135. Szczepankiewicz, B.G.; Ng, P.Y. Sirtuin modulators: targets for metabolic diseases and beyond. Curr. Top. Med. Chem., 2008, 8, 1533-44.
136. Lavu, S.; Boss, O.; Elliott, P.J.; Lambert, P.D. Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov., 2008, 7, 841-53.
137. Imai, S.; Kiess, W. Therapeutic potential of SIRT1 and NAMPTmediated NAD biosynthesis in type 2 diabetes. Front. Biosci., 2009, 14, 2983-95.
138. Schemies, J.; Uciechowska, U.; Sippl, W.; Jung, M. NAD(+)-dependent histone deacetylases (sirtuins) as novel therapeutic targets. Med. Res. Rev., 2010, 30, 861-89.
139. Alcaín, F.J.; Villalba, J.M. Sirtuin inhibitors. Expert Opin. Ther. Pat., 2009, 19, 283-94.
140. Schemies, J.; Sippl, W.; Jung, M. Histone deacetylase inhibitors that target tubulin. Cancer Lett., 2009, 280, 222-32.
141. Balcerczyk, A.; Pirola, L. Therapeutic potential of activators and inhibitors of sirtuins. Biofactors, 2010, 36, 383-93.
142. de Oliveira, R.M.; Pais, T.F.; Outeiro, T.F. Sirtuins: common targets in aging and in neurodegeneration. Curr. Drug Targets, 2010, 11, 1270-80.
143. Silva, J.P.; Wahlestedt, C. Role of Sirtuin 1 in metabolic regulation. Drug Discov. Today, 2010, 15, 781-91.
144. Cen, Y. Sirtuins inhibitors: the approach to affinity and selectivity. Biochim. Biophys. Acta, 2010, 1804, 1635-44.
145. Colak, Y.; Ozturk, O.; Senates, E.; Tuncer, I.; Yorulmaz, E.; Adali, G.; Doganay, L.; Enc, F.Y. SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease. Med. Sci. Monit., 2011, 17, HY5-9.
146. Chen, L. Medicinal chemistry of sirtuin inhibitors. Curr. Med. Chem., 2011, 18, 1936-46.
147. Dittenhafer-Reed, K.E.; Feldman, J.L.; Denu, J.M. Catalysis and mechanistic insights into sirtuin activation. Chembiochem, 2011, 12, 281-9.
148. Blum, C.A.; Ellis, J.L.; Loh, C.; Ng, P.Y.; Perni, R.B.; Stein, R.L. SIRT1 modulation as a novel approach to the treatment of diseases of aging. J. Med. Chem., 2011, 54, 417-32.
149. Sauve, A.A.; Schramm, V.L. SIR2: the biochemical mechanism of NAD(+)-dependent protein deacetylation and ADP-ribosyl enzyme intermediates. Curr. Med. Chem., 2004, 11, 807-26.
150. +-dependent histone/protein deactylases. Biochem. Soc. Trans., 2004, 32, 904-9.
151. Marmorstein, R.; Trievel, R.C. Histone modifying enzymes: structures, mechanisms, and specificities. Biochim. Biophys. Acta, 2009, 1789, 58-68.
152. Smith, B.C.; Denu, J.M. Chemical mechanisms of histone lysine and arginine modifications. Biochim. Biophys. Acta, 2009, 1789, 45-57.
153. Sauve, A.A. Sirtuin chemical mechanisms. Biochim. Biophys. Acta, 2010, 1804, 1591-603.
154. Sanders, B.D.; Jackson, B.; Marmorstein, R. Structural basis for sirtuin function: What we know and what we don't. Biochim. Biophys. Acta, 2010, 1804, 1604-16.
155. +-acetyl-lysine analogs. Mol. Biosyst., 2011, 7, 16-28.
156. +-dependent histone/protein deacetylases. Biochemistry, 2004, 43, 9877-87.
157. Smith, B.C.; Denu, J.M. Sir2 protein deacetylases: evidence for chemical intermediates and functions of a conserved histidine. Biochemistry, 2006, 45, 272-82.
158. +glycohydrolase. Biochemistry, 2008, 47, 10227-39.
159. Schapira, M. Structural biology of human metal-dependent histone deacetylases. Handb. Exp. Pharmacol., 2011, 206, 225-40.
160. Polgar, L. Mechanisms of Protease Action, CRC-Press: Boca Raton, 1989.
161. Hawse, W.F.; Hoff, K.G.; Fatkins, D.G.; Daines, A.; Zubkova, O.V.; Schramm, V.L.; Zheng, W.; Wolberger, C. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure, 2008, 16, 1368-77.
162. Hu, P.; Wang, S.; Zhang, Y. Highly dissociative and concerted mechanism for the nicotinamide cleavage reaction in Sir2Tm enzyme suggested by ab initio QM/MM molecular dynamics simulations. J. Am. Chem. Soc., 2008, 130, 16721-8.
163. Liang, Z.; Shi, T.; Ouyang, S.; Li, H.; Yu, K.; Zhu, W.; Luo, C.; Jiang, H. Investigation of the catalytic mechanism of Sir2 enzyme with QM/MM approach: SN1 vs SN2? J. Phys. Chem. B., 2010, 114, 11927-33.
164. Cen, Y.; Sauve, A.A. Transition state of ADP-ribosylation of acetyllysine catalyzed by Archaeoglobus fulgidus Sir2 determined by kinetic isotope effects and computational approaches. J. Am. Chem. Soc., 2010, 132, 12286-98.
165. Sauve, A.A.; Schramm, V.L. Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry, 2003, 42, 9249-56.
166. Jackson, M.D.; Schmidt, M.T.; Oppenheimer, N.J.; Denu, J.M. Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases, J. Biol. Chem., 2003, 278, 50985-98.
167. Landry, J.; Slama, J.T.; Sternglanz, R. Role of NAD(+) in the deacetylase activity of the SIR2-like proteins. Biochem. Biophys. Res. Commun., 2000, 278, 685-90.
168. Bitterman, K.J.; Anderson, R.M.; Cohen, H.Y.; Latorre-Esteves, M.; Sinclair, D.A. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J. Biol. Chem., 2002, 277, 45099-107.
169. Khan, A.N.; Lewis, P.N. Use of substrate analogs and mutagenesis to study substrate binding and catalysis in the Sir2 family of NADdependent protein deacetylases. J. Biol. Chem., 2006, 281, 11702-11.
170. Smith, B.C.; Denu, J.M. Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases. J. Biol. Chem., 2007, 282, 37256-65.
171. Hirsch, B.M.; Du, Z.; Li, X.; Sylvester, J.A.; Wesdemiotis, C.; Wang, Z.; Zheng, W. Potent sirtuin inhibition bestowed by L-2-amino-7-carboxamidoheptanoic acid (L-ACAH), a N-acetyllysine analog. MedChemComm, 2011, 2, 291-9.
172. Avalos, J.L.; Boeke, J.D.; Wolberger, C. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol. Cell, 2004, 13, 639-48.
173. Avalos, J.L.; Celic, I.; Muhammad, S.; Cosgrove, M.S.; Boeke, J.D.; Wolberger, C. Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Mol. Cell, 2002, 10, 523-35.
174. +and acetylated peptide. Structure, 2006, 14, 1231-40.
175. Cosgrove, M.S.; Bever, K.; Avalos, J.L.; Muhammad, S.; Zhang, X.; Wolberger, C. The structural basis of sirtuin substrate affinity. Biochemistry, 2006, 45, 7511-21.
176. Garske, A.L.; Denu, J.M. SIRT1 top 40 hits: use of one-bead, onecompound acetyl-peptide libraries and quantum dots to probe deacetylase specificity. Biochemistry, 2006, 45, 94-101.
177. Jin, L.; Wei, W.; Jiang, Y.; Peng, H.; Cai, J.; Mao, C.; Dai, H.; Choy, W.; Bemis, J.E.; Jirousek, M.R.; Milne, J.C.; Westphal, C.H.; Perni, R.B. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J. Biol. Chem., 2009, 284, 24394-405.
178. +-dependent tubulin deacetylase. Mol. Cell, 2003, 11, 437-44.
179. Fatkins, D.G.; Monnot, A.D.; Zheng, W. N-Thioacetyl-lysine: A multi-facet functional probe for enzymatic protein lysine N-deacetylation. Bioorg. Med. Chem. Lett., 2006, 16, 3651-6.
180. Smith, B.C.; Denu, J.M. Mechanism-based inhibition of sir2 deacetylases by thioacetyl-lysine peptide. Biochemistry, 2007, 46, 14478-86.
181. +cleavage. J. Am. Chem. Soc., 2007, 129, 5802-3.
182. Cheng, Z.; Tang, Y.; Chen, Y.; Kim, S.; Liu, H.; Li, S.S.; Gu, W.; Zhao, Y. Molecular characterization of propionyllysines in nonhistone proteins. Mol. Cell. Proteomics, 2009, 8, 45-52.
183. Heltweg, B.; Dequiedt, F.; Marshall, B.L.; Brauch, C.; Yoshida, M.; Nishino, N.; Verdin, E.; Jung, M. Subtype selective substrates for histone deacetylases. J. Med. Chem., 2004, 47, 5235-43.
184. Garrity, J.; Gardner, J.G.; Hawse, W.; Wolberger, C.; Escalante-Semerena, J.C. N-lysine propionylation controls the activity of propionyl-CoA synthetase. J. Biol. Chem., 2007, 282, 30239-45.
185. Zhu, A.Y.; Zhou, Y.; Khan, S.; Deitsch, K.W.; Hao, Q.; Lin, H. Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine. ACS Chem. Biol., 2012, 7, 155-9.
186. Asaba, T.; Suzuki, T.; Ueda, R.; Tsumoto, H.; Nakagawa, H.; Miyata, N. Inhibition of human sirtuins by in situ generation of an acetylated lysine-ADP-ribose conjugate. J. Am. Chem. Soc., 2009, 131, 6989-96.
187. +-thiocarbamoyl-lysine (TuAcK). Bioorg. Med. Chem. Lett., 2011, 21, 4753-7.
188. Jamonnak, N.; Hirsch, B.M.; Pang, Y.; Zheng, W. Substrate specificity of SIRT1-catalyzed lysine N-deacetylation reaction probed with the side chain modified N-acetyl-lysine analogs. Bioorg. Chem., 2010, 38, 17-25.
189. Walsh, C.T. Suicide substrates: mechanism-based enzyme inactivators. Tetrahedron, 1982, 38, 871-909.
190. +-dependent protein deacetylases. Int. J. Mol. Sci., 2008, 9, 1-11.
191. Kiviranta, P.H.; Suuronen, T.; Wallén, E.A.; Leppänen, J.; Tervonen, J.; Kyrylenko, S.; Salminen, A.; Poso, A.; Jarho, E.M. NNNNNNNNNNNNNN-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors. J. Med. Chem., 2009, 52, 2153-6.
192. Goodman, M.; Ro, S. In Burger's Medicinal Chemistry and Drug Discovery, Vol. 1, Principles and Practice; Wolff, M.E. Ed.; John Wiley & Sons, Inc.: USA, 1995; pp. 803-61.
193. Suzuki, T.; Asaba, T.; Imai, E.; Tsumoto, H.; Nakagawa, H.; Miyata, N. Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine. Bioorg. Med. Chem. Lett., 2009, 19, 5670-2.
194. Hirsch, B.M.; Gallo, C.A.; Du, Z.; Wang, Z.; Zheng, W. Discovery of potent, proteolytically stable, and cell permeable human sirtuin peptidomimetic inhibitors containing N-thioacetyl-lysine. MedChemComm, 2010, 1, 233-8.
195. Huhtiniemi, T.; Salo, H.S.; Suuronen, T.; Poso, A.; Salminen, A.; Leppänen, J.; Jarho, E.; Lahtela-Kakkonen, M. Structure-based design of pseudopeptidic inhibitors for SIRT1 and SIRT2. J. Med. Chem., 2011, 54, 6456-68.
196. Neal, R.A.; Halpert, J. Toxicology of thiono-sulfur compounds. Annu. Rev. Pharmacol. Toxicol., 1982, 22, 321-39.
197. Ruse, M.J.; Waring, R.H. The effect of methimazole on thioamide bioactivation and toxicity. Toxicol. Lett., 1991, 58, 37-41.
198. Cox, D.N.; Davidson, V.P.; Judd, C.E.; Stodgell, C.; Traiger, G.J. The effect of partial hepatectomy on the metabolism, distribution, and nephrotoxicity of para-methylthiobenzamide in the rat. Toxicol. Appl. Pharmacol., 1992, 113, 246-52.
199. Coppola, G.M.; Anjaria, H.; Damon, R.E. Correlation of oxidation potential and toxicity in thiobenzamides. Bioorg. Med. Chem. Lett., 1996, 6, 139-42.
200. Kang, J.S.; Wanibuchi, H.; Morimura, K.; Wongpoomchai, R.; Chusiri, Y.; Gonzalez, F.J.; Fukushima, S. Role of CYP2E1 in thioacetamide-induced mouse hepatotoxicity. Toxicol. Appl. Pharmacol., 2008, 228, 295-300.
201. Holford, N.H.G. In Basic and Clinical Pharmacology; Katzung, B.G.; Masters, S.B.; Trevor, A.J. Ed.; McGraw-Hill Medical: USA, 2009; pp. 37-51.
202. Lemke, T.L. Review of Organic Functional Groups: Introduction to Medicinal Organic Chemistry, Lippincott Williams & Wilkins: USA, 2003.
203. Wasil, M.; Halliwell, B.; Grootveld, M.; Moorhouse, C.P.; Hutchison, D.C.; Baum, H. The specificity of thiourea, dimethylthiourea and dimethyl sulphoxide as scavengers of hydroxyl radicals. Their protection of alpha 1-antiproteinase against inactivation by hypochlorous acid. Biochem. J., 1987, 243, 867-70.
204. Dong, Y.; Venkatachalam, T.K.; Narla, R.K.; Trieu, V.N.; Sudbeck, E.A.; Uckun, F.M. Antioxidant function of phenethyl-5-bromo-pyridyl thiourea compounds with potent anti-HIV activity. Bioorg. Med. Chem. Lett., 2000, 10, 87-90.
205. Takahashi, H.; Nishina, A.; Fukumoto, R.H.; Kimura, H.; Koketsu, M.; Ishihara, H. Selenoureas and thioureas are effective superoxide radical scavengers in vitro. Life Sci., 2005, 76, 2185-92.
206. van der Horst, A.; Tertoolen, L.G.; de Vries-Smits, L.M.; Frye, R.A.; Medema, R.H.; Burgering, B.M. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J. Biol. Chem., 2004, 279, 28873-9.
207. Outeiro, T.F.; Kontopoulos, E.; Altmann, S.M.; Kufareva, I.; Strathearn, K.E.; Amore, A.M.; Volk, C.B.; Maxwell, M.M.; Rochet, J.C.; McLean, P.J.; Young, A.B.; Abagyan, R.; Feany, M.B.; Hyman, B.T.; Kazantsev, A.G. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science, 2007, 317, 516-9.
208. Nie, H.; Chen, H.; Han, J.; Hong, Y.; Ma, Y.; Xia, W.; Ying, W. Silencing of SIRT2 induces cell death and a decrease in the intracellular ATP level of PC12 cells. Int. J. Physiol. Pathophysiol. Pharmacol., 2011, 3, 65-70.
209. Huhtiniemi, T.; Suuronen, T.; Lahtela-Kakkonen, M.; Bruijn, T.; Jääskeläinen, S.; Poso, A.; Salminen, A.; Leppänen, J.; Jarho, E. NNNNNNNNNNNNNN-Modified lysine containing inhibitors for SIRT1 and SIRT2. Bioorg. Med. Chem., 2010, 18, 5616-25.
210. He, B.; Du, J.; Lin, H. Thiosuccinyl Peptides as Sirt5-Specific Inhibitors. J. Am. Chem. Soc., 2012, 134, 1922-5.
211. Milne, J.C.; Lambert, P.D.; Schenk, S.; Carney, D.P.; Smith, J.J.; Gagne, D.J.; Jin, L.; Boss, O.; Perni, R.B.; Vu, C.B.; Bemis, J.E.; Xie, R.; Disch, J.S.; Ng, P.Y.; Nunes, J.J.; Lynch, A.V.; Yang, H.; Galonek, H.; Israelian, K.; Choy, W.; Iffland, A.; Lavu, S.; Medvedik, O.; Sinclair, D.A.; Olefsky, J.M.; Jirousek, M.R.; Elliott, P.J.; Westphal, C.H. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature, 2007, 450, 712-6.
212. Park, S.J.; Ahmad, F.; Philp, A.; Baar, K.; Williams, T.; Luo, H.; Ke, H.; Rehmann, H.; Taussig, R.; Brown, A.L.; Kim, M.K.; Beaven, M.A.; Burgin, A.B.; Manganiello, V.; Chung, J.H. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell, 2012, 148, 421-33.
213. Tennen, R.I.; Michishita-Kioi, E.; Chua, K.F. Finding a target for resveratrol. Cell, 2012, 148, 387-9.
214. Sauve, A.A.; Moir, R.D.; Schramm, V.L.; Willis, I.M. Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition. Mol. Cell, 2005, 17, 595-601.
215. Avalos, J.L.; Bever, K.M.; Wolberger, C. Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme. Mol. Cell, 2005, 17, 855-68.
216. Imai, S.; Armstrong, C.M.; Kaeberlein, M.; Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NADdependent histone deacetylase. Nature, 2000, 403, 795-800.
217. Schlicker, C.; Boanca, G.; Lakshminarasimhan, M.; Steegborn, C. Structure-based development of novel sirtuin inhibitors. Aging (Albany NY), 2011, 3, 852-72.