Sequence-specific photomodification of DNA by an oligonucleotide-phenanthrodihydrodioxin conjugate.
We introduce a new member of a family of photochemically active oligonucleotide conjugates. A Phenanthrodihydrodioxin (PDHD)-based agent was synthesized and covalently linked to a 5'-end of the 9-mer oligonucleotide via a hexamethylene linker. The conjugate hybridized to a complementary 30-nucleotide-long target and efficiently cleaved it in a sequence specific manner. Up to 67% of target was specifically damaged (51% cross-links and 16% direct cleavage). While the photosensitizer alone nonspecifically damaged only Gs in a single-stranded target, its conjugate cross-linked to and damaged also A, T, and C sites in a target in agreement with duplex and triplex formation.
Bendinskas
K G
KG
Center for Photochemical Sciences, Department of Chemistry, Bowling Green State University, Bowling Green, Ohio 43403, USA. Bendinskas.1@nd.edu
Harsch
A
A
Wilson
R M
RM
Midden
W R
WR
D017104:Bacteriophage M13 / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D008027:Light; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry; D010616:Phenanthrenes / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry; D017422:Sequence Analysis, DNA; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D003432:Cross-Linking Reagents; D004279:DNA, Viral; D004147:Dioxins; D009841:Oligonucleotides; D010616:Phenanthrenes; D017319:Photosensitizing Agents; D011809:Quinones