Bio-Synthesis offers methylphosphonate (MP) DNA linkage modification. This modification introduce a electrically neutral methyl phosphonate backbone instead of the standard negative charged phosphodiester linkage. This lack of charge group improve intracellular transport and improve nuclease degradation. These properties enable the use of methyphosphonate modified DNA oligonucleotides to be used for  in in vitro or in vivo antisense1 applications where the extensive exposure to nucleases is inevitable. However methylphsophonate oligo can lower theoligos cellular update2 as well as the ability to hybridize to the target 3 and interferes with activation of RNase H activity4.  A number of antisense5 applications where modified 3' end with a single methylphosphonate cap has been sucessfully used to eliminate exonuclease degradation.  It also can be use as "cap" to prevent DNA priomer extension 6.

Methylphosphonate oligo synthesized by Bio-Synthesis can be combined with other bases and/or sugar modified. These Methyl-oigo  can be specified to have fully modifie substituted or as chimeric backbone as specified by customer. Contact us for methyphosphonate DNA or RNA synthesis.

Product Information


Product Name:

MethylPhosphonate Oligonucleotide Modification


Backbone Modificaiton, Neutral Charge

Modification Code:



Bio-Synthesis Inc. Oligo Structure



Delivery Format:


Shipping Conditions:

Room Temperature

Storage Conditions:

-20°C To -70°C
Oligonucleotides are stable in solution at 4°C for up to 2 weeks. Properly reconstituted material stored at -20°C should be stable for at least 6 months. Dried DNA (when kept at -20°C) in a nuclease-free environment should be stable for years.


  1. Sarin, P.S., Agrawal, S., Civeira, M.P., Goodchild, J., Ikeuchi, T., Zamecnik, P.C. Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates. Proc. Natl. Acad. Sci. USA (1988), 85: 7448-7451.
  2. Blake, K.R., Murakami, A., Spitz, S.A., Glave, S.A., Reddy, M.P., Tso, P.O., Miller, P.S. Hybridization arrest of globin synthesis in rabbit reticulocyte lysates and cells by oligodeoxyribonucleoside methylphosphonates.Biochemistry (1985), 24: 6139-6145.
  3. Kibler-Herzog, L., Zon, G., Uznanski, B., Whittier, G, Wilson, W.D. Duplex stabilities of phosphorothioate, methylphosphonate, and RNA analogs of two DNA 14-mers. Nucleic Acids Res. (1991), 19: 2979-2986.
  4. Walder, J. Antisense DNA and RNA: progress and prospects. Genes Dev. (1988), 2: 502-504.
  5. 5. Prater, C.E., Miller, P.S. 3'-Methylphosphonate-Modified Oligo-2'-O-methylribonucleotides and Their Tat Peptide Conjugates: Uptake and Stability in Mouse Fibroblasts in Culture. Bioconjugate Chem. (2004), 15: 498-507. 6. Niu, H., Xia, J., Lue, N.F. Characterization of the Interaction between the Nuclease and Reverse Transcriptase Activity of the Yeast Telomerase Complex. Mol. Cell. Biol. (2000), 20: 6806-6815.