Chemical aspects of the benzophenone-photo sensitized formation of two lysine-2'-deoxyguanosine cross-links

1-lysine, 5'-ester with 2'-deoxyguanosine (5'-Lys-dGuo), has been synthesized in order to investigate the photosensitized formation of lysine-2'aeoxyguanosine (lysine-dGuo) adducts. The purpose of tethering a lysine residue to the S-hydroxyl group of dGuo was to mimic the close interaction between DNA and amino acids of histones within cells. Benzophenone-mediated photosensitization of 5'-Lys-dGuo in aerated aqueous solution was found to give rise to two main intramolecular adducts involving the a-amino function of the lysine residue and the C8 position of the guanine moiety. The two modified nucleosides were isolated by reversed-phase high-performance liquid chromatography and characterized by extensive spectroscopic measurements including C-13 and H-1 NMR analyses together with fast atom bombardment mass spectroscopy (FAB-MS). They were identified as L-lysine, N-2-[5[(aminoiminomethyl)imino]-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-4-oxoimidazolidmyl]-, intramolecular 1,5/-ester (6) and L-lysine, N-2-[1-(2-deoxy-beta-D-erythro-pentofuranosyl)-4,5-dihydro-4,5-dioxo-1H-imidazol-2-yl]-, intramolecular 1,5'-ester (10). The structure assignment of the two photoadducts is indicative of the occurrence of two mechanisms. One is Likely to involve a nucleophilic substitution of the guanine radical cation by the a-amino group of the lysine residue. On the other hand, the formation of 6 may be explained in terms of an intramolecular addition of the cl-amino function to the 7,8-double bond of a neutral guanine radical.