Structural Characterization of Intact Covalently Linked DNA Adducts by Electrospray Mass Spectrometry

Abstract

Electrospray mass spectrometry has aided the structural characterization of new series of intact covalently linked [DNA-(aromatic compounds)] adducts. The following DNA adducts with modified d-guanosine units were synthesized: d[CGTAC(GBA)], d[(CCACGTTAACGTGG)-(AAF)_n=1–4] and d[(GATTCGTAGCTACGAATC)-(AAF)_n=1–4] and were analyzed by negative electrospray mass spectrometry. These DNA adducts exhibited different series of multiply charged deprotonated molecular anions. The mass spectra so obtained were of the whole molecules, each having a number of negative charges, mostly in the range of -5 to -9. Fragmentations of the multiply charged deprotonated molecular anions formed by the [mer-14(GAAF)_n=1–4] were obtained by controlled collisionally activated dissociation (CAD) initiated by cone voltage fragmentation and afforded diagnostic product anions which confirmed the presence and location of the guanine nucleobase adduct [Gua-C₈-AAF] and allowed bi-directional sequencing of these DNA-carcinogen adducts. Low-energy collision activated dissocation of the precursor multiply charged anion F^8- at m/z 796.72, produced from the [mer-18(GAAF)₄+Na-H] adduct using a high collision energy, provided some characteristic fingerprint product anions.