| abstract |
The present invention provides oligonucleotide analogues incorporating 5-aza-cytosine in the oligonucleotide sequence, eg, in the form of 5-aza-2'-deoxycytidine (decitabine) or 5-aza-cytidine. . In particular, the present invention provides oligonucleotides enriched in decitadine-deoxyguanosine islands (DpG and GpD) that target CpG islands in the human genome, particularly in promoter regions of genes that are susceptible to abnormal hypermethylation. . Such analogs can be used to modulate DNA methylation, such as effective inhibition of cytosine of methylation at the C-5 position. The present invention provides methods for synthesizing such oligonucleotide analogs and methods for regulating nucleic acid methylation. The present invention also provides phosphoramidite building blocks for oligonucleotide synthesis, methods of synthesizing such compounds or compositions, methods of formulation, and methods of administering to treat diseases such as cancer and blood diseases. |