CHEMICAL ASPECTS OF THE BENZOPHENONE-PHOTO SENSITIZED FORMATION OF 2 LYSINE-2'-DEOXYGUANOSINE CROSS-LINKS

1-lysine, 5'-ester with 2'-deoxyguanosine (5'-Lys-dGuo), has been synt hesized in order to investigate the photosensitized formation of lysin e-2'aeoxyguanosine (lysine-dGuo) adducts. The purpose of tethering a l ysine residue to the S-hydroxyl group of dGuo was to mimic the close i nteraction between DNA and amino acids of histones within cells. Benzo phenone-mediated photosensitization of 5'-Lys-dGuo in aerated aqueous solution was found to give rise to two main intramolecular adducts inv olving the a-amino function of the lysine residue and the C8 position of the guanine moiety. The two modified nucleosides were isolated by r eversed-phase high-performance liquid chromatography and characterized by extensive spectroscopic measurements including C-13 and H-1 NMR an alyses together with fast atom bombardment mass spectroscopy (FAB-MS). They were identified as L-lysine, ta-D-erythro-pentofuranosyl)-4-oxoi midazolidmyl]-, intramolecular 1,5/-ester (6) and L-lysine, ranosyl)-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 t he occurrence of two mechanisms. One is Likely to involve a nucleophil ic 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 expla ined in terms of an intramolecular addition of the cl-amino function t o the 7,8-double bond of a neutral guanine radical.