OpenLB
Open Library of Bioscience

Psoralen intercalates into double-stranded DNA and photoreacts mainly with thymines to form monoadducts and interstrand cross-links. We used an oligonucleotide model to demonstrate a novel mechanism: the reversal of Psoralen cross-links by base-catalyzed rearrangement at 90 degrees C (BCR). The BCR reaction is more efficient than the photoreversal reaction. We show that the BCR occurs predominantly on the furan side of a Psoralen cross-link. The cleavage does not result in the breaking of the DNA backbone, and the thymine base freed from the cross-link by the cleavage reaction appears to be unmodified. Similarly, BCR of the furan-side monoadduct of Psoralen removed the Psoralen molecule and regenerated the unaltered native oligonucleotide. The pyrone-side Psoralen monoadduct is relatively resistant to BCR. One can use BCR to perform efficient oligonucleotide-directed, site-specific delivery of a Psoralen monoadduct. As a demonstration of this approach, we have hybridized a 19 base long oligonucleotide vehicle containing a furan-side Psoralen monoadduct to a 56 base long complementary oligonucleotide target strand and formed a specific cross-link at the target site with 365-nm UV. Subsequent BCR released the oligonucleotide vehicle and deposited the Psoralen at the target site.