title: Some properties of the irreversible complexes of nitracrine (ledakrin, C-283) with polynucleotides.
abstract: In the presence of sulfhydryl compounds an anticancer drug nitracrine (NA), 1-nitro-9-aminoalkylacridine derivative forms strong, probably covalent complexes with DNA. It has been found that it binds with similar efficiency to RNA and DNA exhibiting a certain preference for single-stranded structure. At NA/polynucleotide ratio of 0.15 and nucleic acids concentration 100 microgram/ml the numbers of drug molecules bound per 10(3) nucleotides were about 10--13 for native calf thymus DNA, 19--28 for denatured DNA and 23--36 for RNA. Some base specificity to guanine is observed both in polydeoxyribo- and polyribonucleotides. The complexes of NA with DNA and double-stranded synthetic polynucleotides exhibit decreased transcriptional template activity in bacterial RNA synthesis in vitro system except poly(A) synthesis on poly(dA) x poly(dT) which is insensitive to the drug. The drug binding in vitro leads to cross-link formation in DNA as shown by means of ultraviolet spectrophotometry and hydroxylapatite chromatography of heat-denatured NA-DNA complexes. The amount of the double bonds introduced by the drug is however relatively low as compared with cross-linking of irradiated 8-methoxy-psoralen-DNA (MOP-DNA) complexes.
mesh_terms: D000609:Aminoacridines / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D006882:Hydroxyapatites; D008730:Methoxsalen / Q000378:metabolism; D009564:Nitracrine / Q000378:metabolism*; D009691:Nucleic Acid Denaturation; D009695:Nucleic Acid Renaturation; D012313:RNA / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic
chemical_list: D000609:Aminoacridines; D003432:Cross-Linking Reagents; D004277:DNA, Single-Stranded; D006882:Hydroxyapatites; D012313:RNA; D009564:Nitracrine; D004247:DNA; D008730:Methoxsalen