SGMS Meeting 2001: Plenary Lecture

The effect of nucleoside proton affinity and the formation of zwitteironic oligonucleotides

Giovanni Sindona
Dipartimento di Chimica, Università della Calabria, via P. Bucci, cubo 15/c, I-87030 Arcavacata di Rende (CS), Italy

The existence of "zwitterionic" oligonucleotides was first proved in the early sixties from the crystallographic data obtained from an A3 trimer. This structural motif accounts for the electroneutrality of an oligomer bearing basic and acidic sites. With the advent of desorption ionisation (DI) methods such as FAB and MALDI, it became clear that the formation of negative singly-charged gaseous species was not simply due to the neutralisation of (n-1) phosphodiester group of the oligomer backbone (1,2).

The positively charged nucleobases, within gaseous zwitterionic oligonucleotides, could drive the fragmentation of the strands, through the formation of apurinic sites. The proton affinity (PA) of the nucleobases has been considered, therefore, an important parameter for the evaluation of the sequence of a given oligomer.

The PA of wild type and modified nucleosides and nucleobases have determined by Cooks kinetic method (3), with good accuracy and reproducibility. Unless otherwise suggested, it is now clear that the proton affinity of the same nucleobase can be substantially affected by minor modifications in the sugar structure (scheme).

The PA differences can be attributed to the stabilising/destabilising effects of the hydroxyl groups on the development of the positive charge on the nucleobase after protonation. It can not be excluded a PA change of the same nucleobase within a DNA strand, as a function of the environment. However the PA differences between purine and pyrimidine nucleosides is higher than that due to sugar modification. It can be suggested that Guanosine should be the preferred protonation site and also the preferred oxidation site (4) in DNA damaging processes.

1. G. Sindona et al., J. Am. Chem. Soc., 1983, 105, 5607
2. M. L. Gross et al., J. Am. Soc. Mass Spectrom., 2001, 12, 193
3. G. Sindona et al., J. Mass Spectrom., 2000, 35, 139
4. G. Sindona et al., J. Am.Soc. Mass Spectrom. 2001, 12, 176