Fragmentation of Isomeric Intrastrand Crosslink Lesions of DNA in an Ion-Trap Mass Spectrometer

The collision-induced dissociation pathways of isomeric cytosine-guanine and cytosine-adenine intrastrand crosslink-containing dinucleoside monophosphates were investigated with the stable isotope-labeled compounds to gain insights into the effects of chemical structure on the fragmentation pathways of these DNA modifications. A Dimroth-like rearrangement, which was reported for protonated 2'-deoxycytidine and involved the switching of the exocyclic N4 with the ring N3 nitrogen atom, was also observed for the cytosine component in the protonated ions of C[5-8]G, C[5-2]A, and C[5-8]A, but not C[5-N-2]G or C[5-N-6]A. In these two sets of crosslinks, the C5 of cytosine is covalently bonded with. its neighboring purine base via a carbon atom on the aromatic ring and an exocyclic nitrogen atom., respectively. On the contrary, the rearrangement could occur for the deprotonated ions of C[5-N-2]G, C[5-N-6]A, and unmodified cytosine, but not C[5-8]G, C[5-2]A, or C[5-8]A. In addition, ammonia could be lost more readily from C[5-N-2]G and C[5-N-6]A than from C[5-8]G, C[5-2]A, and C[5-8]A. The results from the present study afforded important guidance for the application of mass spectrometry for the structure elucidation of other intrastrand/interstrand crosslink lesions. (J Am Soc Mass Spectrom 2009, 20, 611-617) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry