Collision‐induced dissociation of oligonucleotide anions fully modified at the 2'‐position of the ribose: 2'‐F/‐H and 2'‐F/‐H/‐OMe mix‐mers

Gas‐phase dissociation of various 2'‐position modified oligonucleotide anions has been studied as a function of precursor ion charge state using ion trap and low energy beam‐type collision‐induced dissociation (CID). For a completely 2'‐O‐methyl modified 6‐mer, all possible dissociation channels along the phosphodiester linkage, generating complementary (a‐B)/w‐, b/x‐, c/y‐, d/z‐ion series, were observed with no single dominant type of dissociation pathway. Full sequence information was generated from each charge state via ion trap CID. More sequential fragmentation was noted under beam‐type CID conditions. Comparison with model DNA, in which all 2'‐OH groups are converted to 2'‐H, and RNA anions suggests that the 2'‐OMe substitution stabilizes the phosphodiester linkage with respect to fragmentation relative to both DNA and RNA oligomers. For modified mix‐mer anions, comprised of DNA nucleotides and 2'‐F substituted nucleotides or a mixture of DNA nucleotides and 2'‐O‐methyl (2'‐OMe) and 2'‐F substituted nucleotides, 3'‐side backbone cleavage was found to be inhibited by the 2'‐OMe or 2'‐F modification on the nucleotides under ion trap CID conditions. Thus, the sequence information was limited to the a‐Base/w‐fragments from the cleavage of the 3' C‐O bond of the 2'‐H (DNA) nucleotides. Under beam‐type CID conditions, limited additional cleavage adjacent to 2'‐OMe substituted nucleotides was noted but 2'‐F modified residues remained resistant to cleavage. Copyright © 2012 John Wiley & Sons, Ltd.