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



Per Base Pricing
5.0 µmole $75.00
10 µmole $100.00
15 µmole $125.00
($150 minimum*)
Minimum pricing requirements may apply. Please request a quote for exact pricing or contact us to speak with a customer service representative.

*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.

Click here to request an oligonucleotide synthesis quotation.

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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