Oligonucleotide analogues are provided that incorporate 5-aza-cytosine in
the oligonucleotide sequence, e.g., in the form of 5-aza-2'-deoxycytidine
(decitabine) or 5-aza-cytidine. In particular, oligonucleotide analogues
rich in decitabine-deoxyguanosine islets (DpG and GpD) are provided to
target the CpG islets in the human genome, especially in the promoter
regions of genes susceptible to aberrant hypermethylation. Such analogues
can be used for modulation of DNA methylation, such as effective
inhibition of methylation of cytosine at the C-5 position. Methods for
synthesizing these oligonucleotide analogues and for modulating nucleic
acid methylation are provided. Also provided are phosphoramidite building
blocks for synthesizing the oligonucleotide analogues, methods for
synthesizing, formulating and administering these compounds or
compositions to treat conditions, such as cancer and hematological
disorders.