Isolation and characterization of pyrimidine-psoralen photoadducts from DNA

Abstract

In this study, we have examined the photoadducts of 4'-hydroxymethyl-4,5',8-trirnethylpsoralen (HMT) and native DNA. Five nucleoside-HMT monoaddition products have been isolated and characterized, corresponding to three deoxythymidine-HMT and two deoxyuridine (derived from deoxycytidine)-HMT adducts. Structural assignments are based on high resolution mass spectrometry and <sup>1</sup>H NMR studies, including homonuclear spin decoupling and nuclear Overhauser effect (NOE) experiments. Our results indicate that (1) a limited number of nucleoside-psoralen adducts are formed with native, double-stranded DNA, and (2) the stereochemistry of the adducts is apparently determined by the geometry of the non-covalent intercalative complex formed by HMT and DNA prior to irradiation.