Photolytic cleavage of DNA by nitrobenzamido ligands linked to 9-aminoacridines gives DNA polymerase substrates in a wavelength-dependent reaction

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Bioconjugate Chemistry; (United States)

DOI:https://doi.org/10.1021/bc00007a010· OSTI ID:5016381

Nielsen, P E; Egholm, M; Koch, T; Christensen, J B; Buchardt, O ^[1]

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1. University of Copenhagen, Department of Biochemistry B, Panum Institute (Denmark)

A series of reagents containing 3- or 4-nitrobenzamido ligands tethered to 9-aminoacridine via variable-length linkers have been prepared and their properties as photochemical DNA cleavers (photonucleases) examined. When irradiated with approximately 300-nm light, where the nitrobenzamido ligand can absorb, they cleave DNA in an oxygen-independent reaction presumably involving oxygen transfer from the nitro group to the deoxyribose units of the DNA backbone. This reaction is pH independent and only slightly affected by the linker length, and the DNA fragments are not substrates for DNA polymerase. When approximately 420-nm light is used, were only the 9-aminoacridinyl ligands absorb, the DNA cleavage is also oxygen-independent but pH dependent, requires DNA saturation with the reagent (base pair:reagent less than or equal to 2), and is most efficient with the longer linkers. The cleavage is specific for guanine residues and results in 5{prime}-phosphate termini and heterogeneous (more than four products) 3{prime}-termini. One of the products is presumably 3{prime}-hydroxy since DNA photocleaved with nitrobenzamido acridine reagents and 420-nm radiation are substrates for DNA polymerase in a nick translation assay as well as for the Klenow fragment. An electron-transfer mechanism is suggested.

• OSTI ID: 5016381
• Journal Information: Bioconjugate Chemistry; (United States), Vol. 2:1; ISSN 1043-1802
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ACRIDINES
BIOLOGICAL EFFECTS
DNA
CLEAVAGE
NITRO COMPOUNDS
DNA POLYMERASES
ELECTRON TRANSFER
ESCHERICHIA COLI
LIGANDS
PHOSPHORUS ISOTOPES
PHOTOCHEMISTRY
PLASMIDS
REAGENTS
SUBSTRATES
TRACER TECHNIQUES
AROMATICS
AZAARENES
AZINES
BACTERIA
CELL CONSTITUENTS
CHEMISTRY
CRYSTAL STRUCTURE
ENZYMES
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
MICROORGANISMS
MICROSTRUCTURE
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PYRIDINES
TRANSFERASES
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