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FEBS Letters Apr 1984The DNA binding characteristics of a mono-, di- and trimeric derivative of 9-aminoacridine were studied. The length of the linking carboxamidoalkyl chains was selected... (Comparative Study)
Comparative Study
The DNA binding characteristics of a mono-, di- and trimeric derivative of 9-aminoacridine were studied. The length of the linking carboxamidoalkyl chains was selected to allow bis- or tris-intercalation according to the excluded-site model. Measurements of DNA unwinding angle using closed circular DNA showed that the trimeric derivative behaves as a tris-intercalating agent. Nevertheless the increase of DNA binding affinity on going from dimer to trimer was found to be relatively small. This is probably related to the large structural constraint for DNA binding of the trimeric derivative. The nature of the linking chain for the design of high-affinity DNA poly-intercalating agents appears therefore critical.
Topics: Aminacrine; Aminoacridines; Animals; Cattle; DNA; Fluorometry; Macromolecular Substances; Poly dA-dT; Viscosity
PubMed: 6714420
DOI: 10.1016/0014-5793(84)80302-6 -
Enhancement of mutagenic activity of 9-aminoacridine by introducing a nitro group into the molecule.Bioscience, Biotechnology, and... Aug 1994Mutagenic activity and DNA intercalation were examined for 9-aminoacridine (9-AA) and its derivatives. Introduction of a nitro group into the 9-AA molecule was found to...
Mutagenic activity and DNA intercalation were examined for 9-aminoacridine (9-AA) and its derivatives. Introduction of a nitro group into the 9-AA molecule was found to enhance the activity enormously as was detected by the Ames test. Acetylation of amino group at 9-position of acridine ring inhibited the intercalation, the frameshift activity disappearing. Rat liver S9 converted 9-AA metabolically to 9-amino-2-hydroxyacridine.
Topics: Acetylation; Aminacrine; Animals; Chromatography, Thin Layer; DNA Damage; Hydroxylation; Magnetic Resonance Spectroscopy; Microsomes, Liver; Mutagenesis; Mutagenicity Tests; Mutagens; Nitro Compounds; Rats; Spectrophotometry, Ultraviolet
PubMed: 7765272
DOI: 10.1271/bbb.58.1420 -
The Journal of Biological Chemistry Jan 1954
Topics: Acridines; Aminacrine; Coloring Agents; Nucleic Acids; Nucleoproteins
PubMed: 13130524
DOI: No ID Found -
Nucleic Acids Research Jun 1987The effects of anti-messenger oligodeoxynucleotides, covalently linked to an intercalating agent, on translation of rabbit beta-globin mRNA, were investigated both in...
The effects of anti-messenger oligodeoxynucleotides, covalently linked to an intercalating agent, on translation of rabbit beta-globin mRNA, were investigated both in wheat germ extract and in microinjected Xenopus oocytes. A specific inhibition of beta-globin synthesis was observed in both expression systems with a modified 11-mer covalently linked to an acridine derivative. In injected oocytes a more efficient block was observed with this modified oligonucleotide than with its unsubstituted homolog. This was ascribed to stacking interactions of the intercalating agent with base pairs which provide an additional stabilization of the [mRNA/DNA] hybrid. We demonstrated that in wheat germ extract, the modified and unmodified oligonucleotides behaved similarly due to the presence of a high RNaseH activity. RNaseH was also present, although to a lesser extent, in the oocyte cytoplasm. This anti-messenger DNA-induced degradation of target mRNA resulted in amplified efficiency of hybrid-arrested translation. This additional mechanism might provide anti-sense DNAs with an advantage over anti-sense RNAs.
Topics: Aminacrine; Animals; Cell-Free System; DNA; Depression, Chemical; Endoribonucleases; Female; Globins; Intercalating Agents; Nucleic Acid Hybridization; Oligodeoxyribonucleotides; Oocytes; Protein Biosynthesis; RNA, Messenger; Rabbits; Ribonuclease H; Triticum; Xenopus
PubMed: 3037483
DOI: 10.1093/nar/15.12.4717 -
The Journal of Biological Chemistry Aug 1982DNA strand breaks produced by damaging agents such as x-ray generally stimulate poly(adenosine diphosphoribose) (ADP-R) synthesis in mammalian cells. DNA intercalating...
DNA strand breaks produced by damaging agents such as x-ray generally stimulate poly(adenosine diphosphoribose) (ADP-R) synthesis in mammalian cells. DNA intercalating agents induce the formation of strand breaks which are unusual in that they are associated with tightly or covalently bound protein. In order to determine whether the intercalator-induced strand breaks are associated with poly-(ADP-R) synthesis, L1210 cells were treated with the intercalating agent, 4'-(9-acridinylamino)methanesulfon-m-anisidide. Poly(ADP-R) synthesis, measured by [3H]NAD incorporation following cell permeabilization, was enhanced in x-irradiated cells, but not in cells exposed to 4'-(9-acridinylamino)methanesulfon-m-anisidide at doses which produced equivalent strand breaks frequencies. The permeabilized cell system did not support DNA synthesis and x-ray-induced strand breaks did not reseal. The intercalator-induced strand breaks, however, resealed within 10 min. Hence, the strand breaks observed in intercalator-treated cells may not constitute DNA damage in the usual sense. The resealing of intercalator-induced DNA breaks in the absence of DNA or poly(ADP-R) synthesis is unique among chemical or physical agents which produce DNA scissions.
Topics: Aminacrine; Aminoacridines; Animals; Cell Membrane Permeability; DNA; DNA Repair; Leukemia L1210; Mice; NAD; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose
PubMed: 7096345
DOI: No ID Found -
Journal of Bacteriology Jul 1986A mutant of Salmonella typhimurium LT2 deficient in methylation of the adenine residues in the sequence 5'-GATC-3' was isolated. The mutation (dam-1) was linked to the...
A mutant of Salmonella typhimurium LT2 deficient in methylation of the adenine residues in the sequence 5'-GATC-3' was isolated. The mutation (dam-1) was linked to the cysG locus, and the properties of the mutant were similar to those of Escherichia coli dam mutants. Reversion of the hisC3076 frameshift marker by 9-aminoacridine was substantially enhanced by the dam-1 mutation, implying a direct role for adenine methylation in the prevention of frameshift mutation induction.
Topics: Adenine; Aminacrine; DNA, Bacterial; Genes, Bacterial; Methylation; Methyltransferases; Mutation; Salmonella typhimurium; Site-Specific DNA-Methyltransferase (Adenine-Specific)
PubMed: 3522556
DOI: 10.1128/jb.167.1.420-422.1986 -
The Journal of Biological Chemistry May 1991Alkalinization-induced Ca2+ release from isolated frog or rabbit sarcoplasmic reticulum vesicles appears to consist of two distinct components: 1) a direct activation of...
Alkalinization-induced Ca2+ release from isolated frog or rabbit sarcoplasmic reticulum vesicles appears to consist of two distinct components: 1) a direct activation of ruthenium red-sensitive Ca2+ release channels in terminal cisternae and 2) an increased ruthenium red-insensitive Ca2+ efflux through some other efflux pathway distributed throughout the sarcoplasmic reticulum. The first of these releases exhibits an alkalinization-induced inactivation process and does not depend on the ruthenium red-insensitive form of Ca2+ release as a triggering agent for secondary Ca(2+)-induced Ca2+ release. Both releases are inhibited when the extravesicular (i.e. cytoplasmic) free [Ca2+] is reduced. This may reflect an increased sensitivity of the Ca2+ release channels to Ca2+ at alkaline pH. The pH sensitivity of the ruthenium red-sensitive Ca2+ release channels could be of significance during excitation-contraction coupling. The ruthenium red-insensitive form of Ca2+ release is less likely to be physiologically relevant, but it probably has contributed greatly to reports of alkalinization-induced decreases in net sarcoplasmic reticulum Ca2+ uptake, particularly under conditions where oxalate supported Ca2+ uptake is much less affected, as here.
Topics: Aminacrine; Animals; Barium; Biological Transport, Active; Calcium; Calcium Channels; Calcium-Transporting ATPases; Cell Compartmentation; Cell-Free System; Dithiothreitol; Glutathione; Hydrogen-Ion Concentration; In Vitro Techniques; Intracellular Membranes; Permeability; Rabbits; Ranidae; Ruthenium Red; Sarcoplasmic Reticulum; Tetracaine
PubMed: 1709160
DOI: No ID Found -
British Journal of Pharmacology and... Sep 1948
Topics: Aminacrine; Lymphogranuloma Venereum; Psittacosis; Viruses
PubMed: 18883997
DOI: 10.1111/j.1476-5381.1948.tb00372.x -
British Journal of Cancer Jan 1987Fluorescence probes for the active centre of an enzyme associated with tumour cells have been used to locate leukaemia cells in a model rat system. These fluorescent...
Fluorescence probes for the active centre of an enzyme associated with tumour cells have been used to locate leukaemia cells in a model rat system. These fluorescent techniques are inexpensive and rapid to carry out. The leukaemic cells can be located by fluorescence microscopy in frozen sections, wax embedded sections and resin embedded sections. The technique is illustrated with reference to sections of leukaemic rat kidney, epididymis and testis. These studies confirm earlier histological findings employing conventional staining techniques and have the advantage that individual leukaemia cells can be detected in leukaemic animals undergoing drug therapy. The evidence suggests that these techniques will be of value in further studies of the design of drugs directed to leukaemia cells.
Topics: Aminacrine; Animals; Epididymis; Fluorescent Dyes; Kidney Neoplasms; Leukemia, Experimental; Lymphocytes; Male; Propidium; Rats; Rats, Inbred Strains; Remission Induction; Testicular Neoplasms; Tosyllysine Chloromethyl Ketone
PubMed: 3814472
DOI: 10.1038/bjc.1987.6 -
Nucleic Acids Research Nov 1987Oligo-heptathymidylates covalently linked to porphyrins bind to complementary sequences and can induce local damages on the target molecule. In dark reactions, iron...
Oligo-heptathymidylates covalently linked to porphyrins bind to complementary sequences and can induce local damages on the target molecule. In dark reactions, iron porphyrin derivatives exhibited various chemical reactivities resulting in base oxidation, crosslinking and chain scission reactions. Reactions induced by reductants, such as ascorbic acid, dithiothreitol or mercapto-propionic acid, led to very localised reactions. A single base was the target for more than 50% of the damages. Oxidising agents such as H2O2 and its alkyl derivatives induced reactions that extended to a wider range of altered bases. The specificity of the chemical modifications observed in these systems is discussed from a mechanistic point of view.
Topics: Alkylating Agents; Aminacrine; Ascorbic Acid; Cross-Linking Reagents; DNA Damage; Dithiothreitol; Hydrogen Peroxide; Metalloporphyrins; NAD; Oxidation-Reduction; Poly T; Polydeoxyribonucleotides; Sulfhydryl Compounds
PubMed: 3684568
DOI: 10.1093/nar/15.21.8643