Effect of O(2′)‐methylation on the stability of polynucleotide helices

The effect of ribose(O2′)‐methylation on the stability of (O2′)‐methylated polyribonucleotide helices has been studied by conformational energy calculations. The preferred orientation of the methyl group is found to further stabilize the helical phosphodiester conformation ( g − , g − ) due to the enhanced short‐range interactions arising between the methyl groups and the adjacent ribose moieties. The experimentally observed increase in melting temperature of (O2′)‐alkylated polyribonucleotides is thus attributable to the enhanced stability of the helical backbone conformation.