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Potent Inhibition of Hha I DNA Methylase by the Aglycon of 2‐(1 H )‐Pyrimidinone Riboside (Zebularine) at the G C GC Recognition Domain
Author(s) -
MARQUEZ VICTOR E.,
ERITJA RAMON,
KELLEY JAMES A.,
VANBEMMEL DANA,
CHRISTMAN JUDITH K.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1281.014
Subject(s) - chemistry , riboside , dna methyltransferase , dna , methyltransferase , biochemistry , stereochemistry , biophysics , methylation , biology
A bstract : A short oligodeoxynucleotide (ODN) with 2‐(1H)‐pyrimidinone at the Hha I 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.