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You are at: All > Oligonucleotides > Custom Oligonucleotide Components > Custom Oligonucleotide Components by Type > Backbones (Purification Options & Expected Yields)

Methylphosphonate
MP

Methylphosphonate

Per Base Pricing
0.2 µmole N/A
1.0 µmole $35.00
5.0 µmole $75.00
10 µmole $100.00
15 µmole $125.00
($150 minimum*)
*Minimum refers only to the portion of the oligonucleotide with the methylphosphonate modification. This is to cover the additional deprotection processing required for this modification.

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Methylphosphonate (MP) modified oligonucleotides were one of the first of the highly modified backbones to get significant attention from those developing antisense oligos. Introduced to the field by Profs. Paul T’so and Paul Miller of Johns Hopkins University in the late 1970’s, the compound became the lead candidate for development by one of the early entrants into the commercialization of oligonucleotide therapeutics, Genta of San Diego.

Methylphosphonate oligos offer two main advantages: a neutral backbone and extremely high stability to nuclease degradation. It was thought that a neutral backbone would facilitate the passage of the oligo into the cell. Unfortunately, this did not turn out to be the case. These modified oligonucleotides were instead sequestered in endosomes, rendering them inactive. Initially, this endosomal punctuate pattern was viewed as highly favorable and proof of effective delivery.

There are two major disadvantages as well. The modification severely affected the ability of the oligonucleotide to hybridize to the target. The reduction in Tm could be mitigated by using a chirally pure molecule (Rp configuration), however this was too costly to consider as a viable commercial option. This was largely the reason for the failure of the backbone to become popular. Another disadvantage is the solubility of the oligo is compromised as MP linkages are added.

That said, there are still a number of applications were complete resistance to nuclease degradation is required, or a neutral backbone is desirous. In those cases, methylphosphonate modifications may be the answer. TriLink is one of the few companies that offer such unusual compounds. The principals of the firm all matriculated from the laboratories of Genta, where they optimized the synthesis and purification of methylphosphonate oligos. If you need a methylphosphonate modified oligonucleotide, TriLink is the best source.

Purification Methods and Expected Yields



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Reference(s)
Stauss-Soukup, J.K., Vaghefi, M.M., Hogrefe, R.I. & Maher, L.J. Effects of neutralization pattern and stereochemistry on DNA bending by methylphosphonate substitution.(1997) Biochemistry 36, (29):8692-8698.
Reynolds, Hogrefe, Jaeger, Schwartz, Riley, Marvin, Daily, Vaghefi, Beck, Knowles, Klem, Arnold. Synthesis and thermodynamics of oligonucleotides containing chirally pure RP methylphosphonate linkages.(1996) Nucleic Acids Research 24, (22):4584-4591.
Trapane, T.L., Hogrefe, R.I., Reynolds, M.A., Kan, L.-S., & Ts’o, P.O.P. Interstrand complex formation of purine oligonucleotides and their nonionic analogs: The model system of d(AG)8 and its compliment d(CT)8 (1996) Biochemistry 35, 5495-5508.
Reynolds, Arnold, Almazon, Beck, Hogrefe, Metzler, Stoughton, Tseng, Trapane, Tso, Woolf. Triple-strand-forming methylphosphonate oligodeoxynucleotides targeted to mRNA efficiently block protein synthesis.(1994) Proc. National Acad. Sci. 91, 12433-12437.
Kulka, M., Smith, C.C., Levis, J., Fishelevich, R., Hunter, J.C.R., Cushman, C.D., Miller, P.S., Ts'o, P.O.P. & Aurelian, L. Synergistic antiviral activities of oligo methylphosphonates .(1994) Antimicrobial Agents and Chemotherapy 38, (4):675-680.
Tari, A.M., Tucker, S.D., Deisseroth, A. & Lopez-Berestein, G. Liposomal Delivery of Methylphosphonate Antisense Oligodeoxynucleotides in Chronic Myelogenous Leukemia.(1994) Blood 84, (2):601-607.
Hogrefe, R.I., Vaghefi, M.M., Reynolds, M.A., Young, K.M. & Arnold, L.J. Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure.(1993b) Nucleic Acids Research 21, (9):2031-2038.
Wickstrom, E., Bacon, T.A. & Wickstrom, E.L. Down-regulation of c-myc antigen expression in lymphocytes of Eu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates.(1992) Cancer Research 52, (December):6741-6745.
Kibler-Herzog, L., Kell, B., Zon, G., Shinozuka, K., Mizan, S. & Wilson, W.D. Sequence dependent effects in methylphosphonate deoxyribonucleotide double and triple helical complexes.(1990) Nucleic Acids Research 18, (12):3545-3555.
Maher, L.J. & Dolnick, B.J. Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylphosphonates in a cell-free system.(1988) Nucleic Acids Research 16, (8):3341-3358.
Sarin, P.S., Agrawal, S., Civeira, M.P., Goodchild, J., Ikeuchi, T. & Zamecnik, P.C. Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates.(1988) Proc. Natl. Acad. Sci. USA 85, 7448-7451.
Agrawal, S. & Goodchild, J. Oligodeoxynucleoside methylphosphonates: synthesis and enzymic degradation.(1987) Tetrahedron Letters 28, (31):3539-3542.
Blake, K., Murakami, A., Spitz, S.A., Glave, S.A., Reddy, M.P., Ts'o, P.O.P. & Miller, P.S. Hybridization Arrest of Globin Synthesis in Rabbit Reticulocyte Lysates and Cell by Oligodeoxyribonucleoside Methylphosphonates.(1985) Biochemistry 24, 6139-6145.
Miller, P.S., Agris, C., Aurelian, L., Blake, K.R., Murakami, A., Reddy, M.P., Spitz, S.A. & Ts'o, P.O.P. Control of ribonucleic acid function by oligonucleoside methylphosphonates.(1985) Biochimie 67, 769-776.
Miller, P.S., McParland, K.B., Jayaraman, K. & Ts'o, P.O.P. Biochemical and biological effects of nonionic nucleic acid methylphosphonates.(1981) Biochemistry 20, 1874-1880.


 

 


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