Alkali reversal of psoralen cross-link for the targeted delivery of psoralen monoadduct lesion
Psoralen intercalates into double-stranded DNA and photoreacts mainly with thymines to form monoadducts and interstrand cross-links. The authors used an oligonucleotide model to demonstrate a novel mechanism: the reversal of psoralen cross-links by base-catalyzed rearrangement at 90/sup 0/C (BCR). The BCR reaction is more efficient than the photoreversal reaction. They 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 based 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, they 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.
- Research Organization:
- Institute for Cancer Research, Philadelphia, PA (USA)
- OSTI ID:
- 6464916
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:17; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
ANTICOAGULANTS
ATP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMICAL REACTIONS
CHEMISTRY
COUMARINS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DNA
DNA ADDUCTS
DRUGS
ELECTROMAGNETIC RADIATION
ELECTROPHORESIS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
ISOTOPES
LIGHT NUCLEI
NEAR ULTRAVIOLET RADIATION
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOTOCHEMISTRY
POLYMERIZATION
PSORALEN
RADIATIONS
RADIOISOTOPES
ULTRAVIOLET RADIATION