Nucleotides LXIV[1]: synthesis hydridization and enzymatic degradation studies of 2'-O-methyloligoribonucleotides and 2'-O-methyl/deoxy gapmers.

2'-O-Methyloligoribonucleotides, deoxyoligonucleotides and 2'-O-methyl/deoxy gapmers were synthesized using solid phase phosphoramidite chemistry employing the 2-(4-nitrophenyl)ethyl (npe) protection strategy. Melting temperatures of the synthesized oligonucleotides as well as their stability against degradation by several different nucleases were determined. 2'-O-Methyloligoribonucleotides showed the highest melting temperatures (Tm's) whereas 2'-O-methyl/deoxy gapmers revealed either slightly higher or surprizingly no thermal stabilities compared with their deoxy analogs when using self-complementary sequences. Gapmers with four 2'-O-methyl nucleotides on both ends showed about the same stability as all 2'-O-methyloligoribonucleotides against micrococal nuclease, nuclease S1, and snake venom phosphodiesterase.