SITE-SPECIFIC LITHIUM ION ATTACHMENT DIRECTS LOW-ENERGY DISSOCIATION PATHWAYS OF DINUCLEOTIDES IN THE GAS-PHASE - APPLICATION TO NUCLEIC-ACID SEQUENCING BY MASS-SPECTROMETRY

Fourier transform ion cyclotron resonance mass spectroscopy has been u sed to examine the low-energy collision-induced dissociation pathways of lithiated dinucleotides. Collisional activation using continuous of f-resonance excitation permits observation of energetically-favorable dissociation pathways. Dissociation products were examined under multi ple collision conditions for center of mass collision energies from 0 eV to the minimum energy required to bring about complete dissociation of the reactant ion (7.0 eV). The lithiated molecular ions dissociate to yield several characteristic products. The major fragmentation pat hways observed in most systems are directed by localization of charge on the phosphate moiety leading to cleavage of the 3'-phosphate dieste r linkage to produce the 3'-sequence ion. In some systems, loss of the 5'-terminus base from the lithiated parent ion is also observed. Exce ptions are observed only in systems where guanine is the 3'-terminus b ase. In these systems, the major products observed are the ion resulti ng from loss of the neutral 3'-terminus base along with its dehydrated decedent ion, the 5'-sequence ion and the ion resulting from loss of water from the 5'-sequence ion. Reaction mechanisms which account for the observed products are proposed. The present results suggest that c ollisional activation of lithiated oligonucleotides may provide useful sequence information. (C) 1997 Elsevier Science B.V.