OLIGODEOXYNUCLEOTIDE ANALOGS CONTAINING 3'-DEOXY-3'-C-THREO-HYDROXYMETHYLTHYMIDINE - SYNTHESIS HYBRIDIZATION PROPERTIES AND ENZYMATIC STABILITY

Novel Oligodeoxynucleotide analogues containing 3'-C-threo-methylene phosphodiester internucleoside linkages were synthesized on automated DNA synthesizers using the phosphoramidite approach. The sugar modified phosphoramidite building block 5 was obtained by phosphitylation of 1-(2,3-dideoxy-5-0-(4,4'-dimethoxtrityl)-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)thymine (4) which was synthesized in only three steps from 5'-0-(4,4'-dimethoxytrityl)thymidine (1). The hybridization properties and enzymatic stability of the oligonucleotide analogues were studied by W experiments. 17-Mers having one or three modifications in the middle or two modifications in each end hybridized to DNA with moderate lowered affinity compared to unmodified 17-mers (Delta T-m 1-3 degrees C per modification). Furthermore, the end-modified and all-modified oligonucleotides were stable towards snake venom phosphodiesterase.