Key featuresShow Hide
- Me-phosphonate linkages are uncharged and nuclease resistant.
- Can be used for targeted cellular delivery of antisense therapeutic agents. Among the first modified oligonucleotides shown to inhibit protein synthesis via an antisense mechanism.
- Synthesis using these monomers requires a low water content oxidiser and changes are necessary from commonly used deprotection procedures because the linkages are more base-labile.
- Should be used in conjunction with standard cyanoethyl phosphoramidites.
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Since methyl (Me) phosphonate linkages are uncharged and nuclease resistant, oligonucleotides containing these have many applications, particularly in developing novel strategies for targeted cellular delivery of antisense therapeutic agents.(1) These were among the first modified oligonucleotides shown to inhibit protein synthesis via an antisense mechanism.
Synthesis using these monomers requires a low water content oxidiser and changes are necessary from commonly used deprotection procedures because the linkages are more base-labile. EDA in 95% EtOH (1:1) is typically used, but other methods have been reported.(2) To help in purification and isolation of these oligos, it is best to incorporate as many phosphodiester linkages (prepared from standard ß-cyanoethyl phosphoramidites) into each oligo as possible.
- See for example: (a) Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylphosphonates in a cell-free system, L.J. Maher, III and B.J. Dolnick, Nucleic Acids Research, 16, 3341-3358, 1988; (b) Solid-phase synthesis of oligo-2-pyrimidinone-2'-deoxyribonucleotides and oligo-2-pyrimidinone-2'-deoxyribose methylphosphonates, Y. Zhou and P.O.P. Ts’o, Nucleic Acids Research, 24, 2652-2659, 1996; and (c) Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs, P. Sazani, S.-H. Kang, M.A. Maier, C. Wei, J. Dillman, J. Summerton, M. Manoharan and R. Kole, Nucleic Acids Research, 19, 3965-3974, 2001.
- Deprotection of methyiphosphonate oligonucleotides using a novel one-pot procedure, R.l. Hogrefe, M.M. Vaghefi, M.A. Reynolds, K.M. Young and L. Arnold Jr, Nucleic Acids Research, 21, 2031-2038, 1993.