Elsevier

Tetrahedron

Volume 49, Issue 48, 1993, Pages 11341-11352
Tetrahedron

Oligodeoxynucleotide analogues containing 3′-deoxy-3′-C-threo-hydroxymethylthymidine: Synthesis, hybridization properties and enzymatic stability

https://doi.org/10.1016/S0040-4020(01)81816-0Get rights and content

Abstract

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-O-(4,4′-dimethoxytrityl)-3-C-hydroxymethyl-β-D-threo-pentofuranosyl)thymine (4) which was synthesized in only three steps from 5′-O-(4,4′-dimethoxytrityl)thymidine (1). The hybridization properties and enzymatic stability of the oligonucleotide analogues were studied by UV 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 (ΔTm 1–3°C per modification). Furthermore, the end-modified and all-modified oligonucleotides were stable towards snake venom phosphodiesterase.

3′-Deoxy-3′-threo-hydroxymethyl nucleoside 4 was stereoselectively synthesized in three steps from 5′-O-(4,4′-dimethoxytrityl)thymidine (1) and subsequently incorporated into oligodeoxynucleotides. Hybridization and enzymatic stability experiments are reported.

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