2’-5’ Linked Oligonucleotides

Cellular DNA and RNA are made up of ribo- and 2’-deoxyribonucleic acids linked together via 3’-5’ phosphodiester linkages and by far comprise the bulk of polynucleic acids found in cells.  Much less common are oligonucleotides which have 2’-5’ linkages.  However, a unique feature of 2’-5’ linked oligonucleotides is their ability to bind selectively to complementary RNA. 
These features suggest a number of interesting uses for 2’-5’ linked oligos such as their use as RNA specific probes or in antisense oligos.  Recently, oligos have been synthesized using 3’-deoxy-2’-phosphoramidites and 2’-deoxy-3’-phosphoramidites to produce  chimeras with 2’-5’ linked ends and 3’-5’ linked central regions.  It was found that 2’-5’ phosphorothioate oligos: 1) bind selectively to complementary RNA with the same affinity as phosphodiester oligos;  2) exhibit much less nonspecific binding to cellular proteins;  3) do not activate RNase H.  A 3’-deoxynucleoside at the 3’-terminus of an otherwise normal oligonucleotide effectively blocks polymerase extension.