Oligonucleotides containing 2'-OMe-5-Me-U (2'-OMe-T), 2'-OMe-N-Ac-5-Me-C or 2'-OMe-I are particularly applicable to triplex and antisense studies using 2'-OMe-RNA. For example, the immune stimulatory activity of CpG containing oligonucleotides in which C or G was substituted with 2'-OMe ribonucleotides, 5-Me-dC, or 2'-OMe-5-Me-C has been studied alone and in combination with TLR agonists. ⁽¹⁾

When 2'-OMe residues are incorporated into triplex forming oligonucleotides ⁽²⁾ (TFOs), similar trends in nuclease resistance and triplex stability are seen as with duplexes.

Hence they have been used to develop TFOs for use as gene targeting reagents.⁽³⁾ Triplex stability can be increased further with the incorporation of 2'-OMe-5-Me-U residues into the oligonucleotide ⁽⁴⁾ using 2'-OMe-5-Me-U. Interestingly, 2'-OMe-5-Me C can have the opposite effect and destabilise the triplex, yet is still more stable than a DNA and/or RNA triplex. Incorporation of both 2'-OMe-5-Me U and 2'-OMe-5-Me C enables fine tuning of the Tm of the resulting triplex.

Ref:

1. Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9, D. Yu, D. Wang, F.-G. Zhu, L. Bhagat, M. Dai, E. R. Kandimalla and S. Agrawal, J. Med. Chem., 52, 5108-5114, 2009.
2. Pyrimidine motif triplexes containing polypurine RNA or DNA with oligo 2'-O-Methyl or DNA triplex forming oligonucleotides, M. Behan and P.S. Miller, Biochim. Biophys. Acta., 1492, 155-162, 2000.
3. The development of bioactive triple helix-forming oligonucleotides, M.M. Seidman, N. Puri, A. Majumdar, B. Cuenoud, P.S. Miller and R. Alam, in volume 1058, Therapeutic Oligonucleotides: Transcriptional and Translational Strategies for Silencing Gene Expression, 119–127, November 2005, Wiley-Blackwell.
4. Effects of 5-methyl substitution in 2'-O-methyl oligo(pyrimidine)nucleotides on triple-helix formation, M. Shimizu, T. Koizumi., H. Inoue and E. Ohstuka, Bioorg. Med. Chem. Letts., 4, 1029-1032, 1994.