Potent Inhibition of HhaI DNA Methylase by the Aglycon of 2-(1H)-Pyrimidinone Riboside (Zebularine) at the GCGC Recognition Domain

Annals of the New York Academy of Sciences

Volumn 1002, Issue , 2003, Pages 154-164

  Marquez, Victor E ^a   Eritja, Ramon ^b   Kelley, James A ^a   Vanbemmel, Dana ^c   Christman, Judith K ^c,d  

^a NATIONAL CANCER INSTITUTE   (United States)

^b DEPT OF ENVIRONMENTAL CHEMISTRY   (Spain)

^c UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^d UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

2 (1H) pyrimidinone; 2 deoxy 5 azacytidine; 5 azacytidine; 5 azacytosine; Cytidine deaminase inhibitor; DNA methyltransferase; Gene reactivation; Methylation inhibitor; Zebularine

Indexed keywords

2 PYRIMIDINE RIBOSIDE; 5 AZA 2' DEOXYCYTIDINE; AGLYCONE; AMINO ACID DERIVATIVE; ANTINEOPLASTIC AGENT; AZACITIDINE; CYTIDINE DEAMINASE INHIBITOR; DNA METHYLTRANSFERASE; GLYCYLCYSTEINYLGLYCYLCYSTEINE; OLIGODEOXYNUCLEOTIDE; UNCLASSIFIED DRUG; ZEBULARINE;

AMINO ACID SUBSTITUTION; ANTINEOPLASTIC ACTIVITY; COMPLEX FORMATION; CONFERENCE PAPER; DRUG ACTIVITY; DRUG EFFECT; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; GENE ACTIVATION; GENE TARGETING; METHYLATION; NONHUMAN; PROTEIN DOMAIN; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; THERMOSTABILITY;

EID: 1342311011     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1196/annals.1281.014     Document Type: Conference Paper

References (41)

1. IKEHARA, M. 1960. Studies on coenzyme analogs. I. Synthesis of 3-β-D-ribofuranosyl-2-oxo-2,3-dihydropyrimidine (6-deoxyuridine) and its 5′-phosphate. Chem. Pharm. Bull. (Tokyo) 8: 308-313.
2. FUNAKOSHI, R., M. IRIE & T. UKITA. 1961. Synthesis of unnatural pyrimidine nucleosides. Chem. Pharm. Bull. (Tokyo) 9: 406-409.
3. OYEN, T.B. 1969. Synthesis and properties of ribosylpyrimidin-2-one. Biochim. Biophys. Acta 186: 237-243.
4. PISCHEL, H., A. HOLY & G. WAGNER. 1972. Glycosyl derivatives of heterocycles. XLV. Ribosyl derivatives of pyrimidinones. Coll. Czech. Chem. Commun. 37: 3475-3482.
5. WIGHTMAN, R.H. & A. HOLY. 1973. Nucleic acid components and their analogs. CLIX. Synthesis of some 2-pyrimidinone nucleosides. Coll. Czech. Chem. Commun. 38: 1381-1386.
6. CECH, D. & A. HOLY. 1977. Nucleic acid components and their analogs. CXC. Preparation of 2-pyrimidinone nucleosides from uracil nucleosides. Coll. Czech. Chem. Commun. 42: 2246-2260.
7. HOLY, A. 1977. Preparation of acyl derivatives of pyrimidine-2-one nucleosides by the silyl variant of the Hubert-Johnson reaction. Coll. Czech. Chem. Commun. 42: 902-908.
8. MCCORMACK, J.J., V.E. MARQUEZ, P.S. LIU, et al. 1980. Inhibition of cytidine deaminase by 2-oxopyrimidine riboside and related compounds. Biochem. Pharmacol. 29: 830-832.
9. SUHADOLNIK, R.J. 1979. In Nucleosides as Biological Probes. Wiley. New York, p. 244.
10. DRISCOLL, J.S., V.E. MARQUEZ, J. PLOWMAN, et al. 1991. Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues. J. Med. Chem. 34: 3280-3284.
11. OYEN, T.B., I. VOTRUBA, A. HOLY & R.H. WIGHTMAN. 1973. Mechanism of inhibition of DNA synthesis in Escherichia coli by pyrimidin-2-one. Biochim. Biophys Acta 324: 14-23.
12. HOLY, A., A. LUDZISA, I. VOTRUBA, et al. 1985. Preparation of analogs of cytosine and 2-pyrimidinone nucleosides and their effect on bacterial (Escherichia coli A19) cytidine aminohydrolase. Coll. Czech. Chem. Commun. 50: 393-417.
13. MAEDA, M., C. KANEKO, N.A. UCHIDA & T. SASAKI. 1985. Synthesis of 1-β-D-ribofuranosyl-1,2-dihydropyrimidin-2-one derivatives and their biological activities. Nucleic Acids Res. Symp. Ser. 16: 77-80.
14. KIM, C.-H., V.E. MARQUEZ, D.T. MAO, et al. 1986. Synthesis of pyrimidine-2-one nucleosides as stable inhibitors of cytidine deaminase. J. Med. Chem. 29: 1374-1380.
15. FRICK, L., C. YANG, V.E. MARQUEZ & R. WOLFENDEN. 1989. Binding of pyrimidin-2-one ribonucleoside by cytidine deaminase as a transition-state analogue 3,4-dihydrouridine and contribution of the 4-hydroxyl group to its binding activity. Biochemistry 28: 9423-9430.
16. BETTS, L., S. XIANG, S.A. SHORT, et al. 1994. Cytidine deaminase. The 2. 3 Å crystal structure of an enzyme:transition state analogue complex. J. Mol. Biol. 235: 635-656.
17. SHORT, S.A., R. WOLFENDEN & C.W. CARTER, JR. 1995. Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase. Biochemistry 34: 4516-4523.
18. KELLEY, J.A., J.S. DRISCOLL, J.J. MCCORMACK, et al. 1986. Furanose-pyranose isomerization of reduced pyrimidine and cyclic urea ribosides. J. Med. Chem. 29: 2351-2358.
19. LALIBERTE, J., V.E. MARQUEZ & R.L. MOMPARLER. 1992. Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2′- deoxycytidine by human cytidine deaminase. Cancer Chemother Pharmacol. 30: 7-11.
20. NATIONAL INSTITUTES OF HEALTH. 1984. In vivo cancer models 1976-1982. NIH publication 84-2635, National Institutes of Health, DHHS, February 1984.
21. BARCHI JR., J.J., A. HACES, V.E. MARQUEZ & J.J. MCCORMACK. 1992. Inhibition of cytidine deaminase by derivatives of 1-(β-D-ribofuranosyl)- dihydropyrimidin-2-one (zebularine). Nucleosides Nucleotides 11: 1781-1793.
22. GREER, S., J. SCHWADE & H.S. MARION. 1995. 5-Chlorodeoxycytidine and biomodulators of its metabolism result in 50-percent to 80-percent cures of advanced Emt-6 tumors when used with fractionated radiation. Int. J. Rad. Oncol. Biol. Biophys. 32: 1059-1069.
23. JONES, P.A. & S.M. TAYLOR. 1980. Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85-93.
24. CHENG, J.C., C.B. MATSEN, F.A. GONZALEZ, et al. 2003. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J. Natl. Cancer Inst. 95: 399-409.
25. LIU, P.S., V.E. MARQUEZ, J.S. DRISCOLL & R.W. FULLER. 1981. Cyclic urea nucleosides. Cytidine deaminase activity as a function of aglycon ring size. J. Med. Chem. 24: 662-666.
26. MARQUEZ, V.E., K.B.V. RAO, J.V. SILVERTON & J.A. KELLEY. 1984. A ring-expanded approach to 1,3-diazepin-2-one nucleosides. J. Org. Chem. 49: 912-919.
27. VOTRUBA, I., A. HOLY & R.H. WIGHTMAN. 1973. Mechanism of inhibition of DNA synthesis in Escherichia coli by pyrimidine-2-one β-D- ribofuranoside. Biochim. Biophys. Acta 324: 14-23.
28. IVANETICH, K.M. & D.V. SANTI. 1992. 5,6-dihydropyrimidine adducts in the reactions and interactions of pyrimidines with proteins. Progress Nucleic Acid Res & Mol. Biol. 42: 127-156.
29. TAYLOR, C., K. FORD, B.A. CONNOLLY & D.P. HORNBY. 1993. Determination of the order of addition of substrates to MspI DNA methyltransferase using a novel mechanism-based inhibitor. Biochem. J. 291: 493-504.
30. FORD, K., C. TAYLOR, B.A. CONNOLLY & D.P. HORNBY. 1993. Effects of co-factor and deoxycytidine substituted oligonucleotides upon sequence-specific interactions between MspI DNA methyltransferase and DNA. J. Mol. Biol. 230: 779-786.
31. HURD, P.J., A.J. WHITMARSH, G.S. BALDWIN, et al. 1999. Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J. Mol. Biol. 286: 389-401.
32. KLIMASAUSKAS, S., S. KUMAR, R.J. ROBERTS & X.D. CHENG. 1994. HhaI Methyltransferase flips its target base out of the DNA helix. Cell 76: 357-369.
33. GILDEA, B. & L.H. MCLAUGHLIN. 1989. The synthesis of 2-pyrimidone nucleosides and their incorporation into oligodeoxynucleotides. Nucleic Acids Res. 17: 2261-2281.
34. ZHOU, L., X. CHENG, B.A. CONNOLLY, et al. 2002. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 321: 591-599.
35. GABBARA, S., D. SHELUHO & A. BHAGWAT. 1995. Cytosine methyltransferase from Escherichia coli in which active site cysteine is replaced with serine is partially active. Biochemistry 34: 8914-8923.
36. BRANK, A.S., R. ERITJA, R. GARCIA-GUIMIL, et al. 2002. Inhibition of HhaI DNA (cytosine-C5) methyltransferase by oligodeoxyribonucleotides containing 5-aza-2′-deoxycytidine: examination of the intertwined roes of co-factor, target, transition-state structure and enzyme conformation. J. Mol. Biol. 323: 53-67.
37. ZHOU, Y. & P.S. TS'O. 1996. Solid-phase synthesis of oligo-2-pyrimidinone-2′-deoxyribonucleotides and oligo-2-pyrimidinone- 2′-deoxyribose methylphosphonates. Nucleic Acids Res. 24: 2652-2659.
38. SHEIKHNEJAD, G., A. BRANK, J.K. CHRISTMAN, et al. 1999. Mechanism of inhibition of DNA (cytosine C5)-methyltransferases by oligodeoxyribonucleotides containing 5,6-dihydro-5-azacytosine. J. Mol. Biol. 285: 2021-2034.
39. BEISLER, J.A. 1978. Isolation, characterization, and properties of a labile hydrolysis product of the antitumor nucleoside, 5-azacytidine. J. Med. Chem. 21: 204-208.
40. BARCHI JR., J.J., S. MUSSER & V.E. MARQUEZ. 1992. The decomposition of 1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) in alkali: mechanism and products. J. Org. Chem. 57: 536-541.
41. JOHNS, D.G. 1974. Metabolism of cancer chemotherapeutic agents via pathways utilized by endogenous substrates. In Antineoplastic and Immunosuppressive Agents I. A.C. Sartorelli & D.G. Johns, Eds.: 270-287. Springer-Verlag. Berlin, Heilderberg, New York.