Photochemical cleavage of DNA by nitrobenzamides linked to 9-aminoacridine.
Nitrobenzamido ligands linked to the DNA intercalator 9-aminoacridine via poly(methylene) chains induce single-strand nicks in DNA upon irradiation with long-wavelength ultraviolet light (lambda greater than or equal to 300 nm). Optimal photocleavage activity was found for the reagent 9-[[6-(4-nitrobenzamido)hexyl]amino]-acridine. Removal of the acridinyl ligand or changing the position of the nitro group from the 4- to the 2-position caused a 10-fold decrease in photocleavage efficiency, whereas a change to the 3-position caused a 30-fold reduction. The DNA cleavage was 5-fold enhanced by subsequent piperidine treatment and showed some sequence dependency with predominant cleavage at G and T residues. Furthermore, significant differences in cleavage preference were observed when the poly(methylene) linker length was changed.
Nielsen
P E
PE
Department of Biochemistry B, Panum Institute, University of Copenhagen, Denmark.
Jeppesen
C
C
Egholm
M
M
Buchardt
O
O
D000609:Aminoacridines / Q000138:chemical synthesis / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D007202:Indicators and Reagents; D009574:Nitro Compounds / Q000494:pharmacology*; D010782:Photolysis; D010957:Plasmids / Q000187:drug effects / Q000528:radiation effects; D013329:Structure-Activity Relationship
D000609:Aminoacridines; D001549:Benzamides; D007202:Indicators and Reagents; D009574:Nitro Compounds; D004247:DNA