An extended phosphate linkage: Synthesis, hybridization and modeling studies of modified oligonucleotides

Article abstract of DOI:10.1080/07328319608002438

Novel stretched oligonucleotides (A-D) containing a 3'-α-C-methylene phosphodiester bridge (5-atoms long) have been synthesized on an automated synthesizer utilizing phosphoramidite chemistry. The key building-block 1- [3''-O-β-cyanoethyldiisopropylaminophosphiryl-2,3-dideoxy-5-O- dimethoxytriphenylmethyl-3-C-(hydroxymethyl)-β-D-erythro- pentofuranosyl]thymine (21) was prepared in a stereoselective manner from thymidine. Hybridization studies indicated a drop (1.8-3.0 °C/mod.) in affinity for the complementary RNA and DNA targets. Molecular modeling results indicated that the 5-atom modified backbone had a different geometry around the phosphodiester linkage compared to the natural phosphodiester linkage. The stretched backbone may not be useful for antisense or triplex constructs, however it may find applications in biochemical/enzyme studies.

Full text of DOI:10.1080/07328319608002438

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An Extended Phosphate Linkage:
Synthesis, Hybridization and Modeling
Studies of Modified Oligonucleotides
Becky Haly a , Laurent Bellon a , Venkatraman Mohan a & Yogesh
Sanghvi a
a Medicinal Chemistry Department , Isis Pharmaceuticals , 2292
Faraday Avenue, Carlsbad, CA, 92008
Published online: 22 Aug 2006.
To cite this article: Becky Haly , Laurent Bellon , Venkatraman Mohan & Yogesh Sanghvi (1996)
An Extended Phosphate Linkage: Synthesis, Hybridization and Modeling Studies of Modified
Oligonucleotides, Nucleosides and Nucleotides, 15:7-8, 1383-1395, DOI: 10.1080/07328319608002438
To link to this article: http://dx.doi.org/10.1080/07328319608002438
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