The psoralen-DNA photoreaction. Characterization of the monoaddition products from 8-methoxypsoralen and 4,5',8-trimethylpsoralen

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Abstract
The isolation and structural characterization are described of the major monoaddition products formed in the photoreaction of two naturally occurring psoralens, 8-methoxypsoralen and 4,5'',8-trimethylpsoralen, with high molecular weight, double-stranded DNA. Hydrolysis of the psoralen-modified DNA and subsequent chromatography resulted in the isolation of 4 modified nucleosides from each psoralen. Structural characterization was accomplished by mass spectrometry and 1H NMR analysis. The major products, accounting for 44-52% of the covalently bound psoralen, are 2 diastereomeric thymidine adducts formed by cycloaddition between the 5,6 double bond of the pyrimidine and the 4'',5'' (furan) double bond of the psoralen. A minor product, < 2% of the covalently bound psoralen, is a furan-side adduct to deoxyuridine, derived from an initially formed deoxycytidine adduct by hydrolytic deamination. A 4th product is a thymidine adduct where cycloaddition has taken place between the 5,6 double bond of the pyrimidine and the 3,4 (pyrone) double bond of the psoralen. This pyrone-side adduct accounts for 19% of the covalently bound 8-methoxypsoralen but for < 3% of the covalently bound 4,5'',8-trimethylpsoralen. All of the isolated adducts have cis-syn stereochemistry. The stereochemistry and product distribution of the adducts are determined in part by the constraints imposed by the DNA helix on the geometry of the noncovalent intercalation complex formed by psoralen and DNA prior to irradiation.