Sodium Controlled Selective Reactivity of Protonated Deoxy-Oligonucleotides in the Gas Phase

Metastable fragmentation of the positively charged, hexameric oligonucleotides 5'-d(TTXYTT) (X and Y are dC, dG, or dA) and 5'-d(CTCGTT), 5'-d(TTCGTC) and 5'-d(CTCGTC) is studied after matrix assisted laser desorption/ionization (MALDI). The influence of the degree of sodiation, i.e., when the acidic protons are one by one exchanged against sodium ions, is systematically studied for the exchange of up to seven protons against sodium ions. Exchanging the acidic protons against sodium gradually quenches the backbone cleavage through the w and a-B channels, and quantitative quenching of these channels is generally achieved with the exchange of four protons against sodium ions. At the same time, the exchange of protons against sodium ions promotes the loss of a neutral, high proton affinity base. The formation of the w and a-B fragments is found to be highly dependent on the sequence of the central bases. A single mechanism consistent with these observations is proposed. In addition to the quenching of the classical w and a-B reaction channels, a drastic and abrupt on/off-switching of new reaction channels is observed as the degree of sodiation successively increases. These channels involve selective loss of the two central bases and the excision of a phosphodiester group and a sugar unit from the center of the oligonucleotides. Synchronously, the two terminal fragments recombine to form a tetramer containing the two terminal nucleosides from each end of the hexamer. Possible mechanism explaining these remarkable channels are discussed. (J Am Soc Mass Spectrom 2009, 20, 689-696) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry