Nucleoside Phosphonic Acids
Our investigation in the area of the chemistry of NPAs has provided an impressive number of novel structurally diverse compounds containing classical furanose and non-oxygen heterocyclic rings. Among them, potent inhibitors of several salvage pathway enzymes were found, e.g. selective inhibitors of human mitochondrial and cytosolic pyrimidine specific 5’(3’)-deoxynucleotidases were recognized.
Modified oligonucleotides containing several types of nucleoside phosphonic acids exhibit significantly increased nuclease stability, enhanced hybridization, and stimulation of RNase H activity. These properties may classify phosphonate oligonucleotides for their potential use in biology as antisense compounds in regulation of gene expression. Our attention is also focused on the chemistry and biology of the modified α-D and α-L-oligodeoxynucleotides—an almost forgotten group of compounds. Of particular interest is a group of pyrrolidine nucleoside phosphonates and 4’-alkoxynucleosides that, upon their incorporation into oligonucleotides, significantly increase duplex stability and discriminate between RNA and DNA targets.