title: Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (zebularine) at the GCGC recognition domain.
abstract: A short oligodeoxynucleotide (ODN) with 2-(1H)-pyrimidinone at the HhaI DNA methyltransferase target site (GCGC) is shown to induce a level of inhibition of methyl transfer and thermal stability of the complex with the enzyme identical to that achieved with a similar ODN substituted with 5-azacytosine. The drugs responsible for these effects-zebularine and 5-azacytidine/2'-deoxy-5-azacytidine-are contrasted in terms of chemical stability and possible metabolic activation by a brief structure-activity analysis.
authors.affiliation: Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, Maryland 21702, USA. marquezv@dc37a.nci.nih.gov
authors.forename: Victor E
authors.initials: VE
authors.lastname: Marquez
authors.forename: Ramon
authors.initials: R
authors.lastname: Eritja
authors.forename: James A
authors.initials: JA
authors.lastname: Kelley
authors.forename: Dana
authors.initials: D
authors.lastname: Vanbemmel
authors.forename: Judith K
authors.initials: JK
authors.lastname: Christman
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D003562:Cytidine / Q000031:analogs & derivatives; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors; D004247:DNA / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors*; D017434:Protein Structure, Tertiary; D011741:Pyrimidine Nucleosides / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011741:Pyrimidine Nucleosides; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D004247:DNA; C037664:DNA modification methylase HhaI; D015257:DNA-Cytosine Methylases; D004248:DNA (Cytosine-5-)-Methyltransferases; D003564:Cytidine Deaminase