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Nature Jun 1976
Topics: Biological Transport; Cell Line; Dactinomycin; Drug Resistance; Liposomes; RNA
PubMed: 934317
DOI: 10.1038/261699a0 -
Antibiotiki Mar 1975Actinomycin D0 differing from actinomycin D in replacement of I residue of sarcosine by glycine in one of the peptide chains was found to have a lower inhibitory effect... (Comparative Study)
Comparative Study
Actinomycin D0 differing from actinomycin D in replacement of I residue of sarcosine by glycine in one of the peptide chains was found to have a lower inhibitory effect on RNA synthesis in various biological systems. On interaction of E. coli with DNA actinomycin D0 formed a complex with DNA having the binding constant K=1.6 with 10-5 which was 100 times lower than the binding constant of actinomycin D. Therefore, actinomycin D0 formed a complex with DNA which was 100 times less stable than actinomycin D. Actinomycins D0, D and II having different conformations in buffer on interaction with DNA formed complexes having similar conformations. The conformational change from free actinomycin to bound actinomycin was found difficult in case of actinomycin D0 because of its slow rate of complex formation with DNA as compared to that of other actinomycins complex formation with DNA.
Topics: Animals; Bacillus subtilis; Binding Sites; Carbon Radioisotopes; Cells, Cultured; Circular Dichroism; Culture Media; DNA; Dactinomycin; Drug Interactions; Escherichia coli; Kidney; Molecular Conformation; RNA; Spectrophotometry; Swine; Tritium; Uridine; Valine
PubMed: 806255
DOI: No ID Found -
Cancer Chemotherapy Reports 1974
Topics: Antineoplastic Agents; Dactinomycin; Fermentation; Hydrolysis; Lactones; Streptomyces; Structure-Activity Relationship; Tritium
PubMed: 4130360
DOI: No ID Found -
Journal of Biochemistry Aug 2006Complexes of actinomycin D (AMD) and 7-amino-actinomycin D (7AAMD) with model hairpin oligonucleotide HP1 and various types of DNA in aqueous solutions were investigated...
Complexes of actinomycin D (AMD) and 7-amino-actinomycin D (7AAMD) with model hairpin oligonucleotide HP1 and various types of DNA in aqueous solutions were investigated by steady-state, polarized, time-resolved and stopped-flow fluorimetry, and photometry. Prompt non-stacking binding of the actinomycins inside HP1 was observed. No energy transfer from nucleotides to 7AAMD in the complex was detected, most likely because of the absence of stacking intercalation. Complex formation of AMD or 7AAMD and HP1 was followed by the transition from a random flexible conformation of the hairpin to a more compact rigid structure, and subsequently to hypochromism. Strong competition between AMD and 7AAMD for a cavity in HP1 was observed. The decrease in the 7AAMD emission after addition of DNA to the 7AAMD/HP1 complex indicates that actinomycins can be redistributed from HP1 to DNA, i.e. hairpin oligonucleotides can serve as molecular carriers of actinomycins.
Topics: DNA; Dactinomycin; Energy Transfer; Fluorescence; Nucleic Acids; Oligonucleotides; Protein Binding
PubMed: 16861251
DOI: 10.1093/jb/mvj150 -
Biopolymers Jul 1979
Topics: Animals; Binding Sites; Cattle; DNA; Dactinomycin; Nucleotides
PubMed: 540129
DOI: 10.1002/bip.1979.360180712 -
Biochemistry Jul 1994A photoreactive analog of actinomycin (7-azidoactinomycin D) has been used in experiments to probe directly the shuffling hypothesis of Fox and Waring [Fox, K. R., &...
A photoreactive analog of actinomycin (7-azidoactinomycin D) has been used in experiments to probe directly the shuffling hypothesis of Fox and Waring [Fox, K. R., & Waring, M. J. (1984) Nucleic Acids Res. 12, 9271-9285]. According to this theory, actinomycin D molecules initially interact with non-sequence-specific sites on DNA and subsequently "shuffle" along the polymer in a one-dimensional migratory fashion so as to locate their preferred sequence-dependent binding sites. In the study presented here, the drug-DNA complex was allowed to equilibrate (in the dark) for various periods of time, followed by photolysis which renders the complex irreversible and traps the ligand at its instantaneous binding sites. Visualization of the piperidine-labile sites and investigation of how the intensity of reaction at each site changes with time can provide direct confirmation of the shuffling hypothesis. The data reveal that actinomycin D does indeed engage in shuffling along the DNA. After only short equilibration times (20 s) actinomycin D is observed to bind to a variety of sites on the DNA, including many which are not regarded as canonical preferred binding sites at equilibrium. However, after longer periods of equilibration the intensity of reaction is shown to drop as a function of time at nonspecific sites, with corresponding increase at sequence-specific sites. In addition, base sequences which flank the intercalation sites can be seen to play a major role in influencing the binding and sequence specificity of actinomycin.
Topics: Base Sequence; Binding Sites; DNA; DNA Damage; Dactinomycin; In Vitro Techniques; Molecular Sequence Data; Photochemistry
PubMed: 8038164
DOI: 10.1021/bi00195a015 -
Cancer Chemotherapy Reports 1975Tissue concentration of 3H-actinomycin D have been determined in the rat, monkey, and dog after an iv dose of 0.6 mg/m2 body surface area. The drug-tissue half-life was...
Tissue concentration of 3H-actinomycin D have been determined in the rat, monkey, and dog after an iv dose of 0.6 mg/m2 body surface area. The drug-tissue half-life was determined for various tissues of the rat, monkey, and dog. A mean drug-tissue half-life of 47 hours was calculated for the tissues of the dog. Exceptions were the testis and brain. Significant concentrations of 3H-actinomycin D failed to accumulate in the brain. Although testis drug concentrations were lower than most other tissues evaluated, the drug-tissue half-life was significantly greater than that of other tissues. In all species studied 3H-actinomycin D was rapidly depleted from serum after iv dosage, with concomitant accumulation of drug in the tissues. 3H-actinomycin D was excreted via the biliary and urinary routes in all species studied. No metabolites of 3H-actinomycin D were detected in the bile or urine of the rat, monkey, or dog with the methods employed. When expressed on a body weight basis, body surface area doses were more than threefold greater in the rat than in the dog. However, the average ratio of concentration X time values (rat C X T/dog C X T) for 11 different tissues of the rat and dog was only 1.3. The results strongly suggest that an equivalent dose of actinomycin D, with dosage based on a body surface area basis, results in nearly equal tissue-drug exposure for most tissues in various mammalian species.
Topics: Animals; Bile; Body Surface Area; Dactinomycin; Dogs; Half-Life; Haplorhini; Macaca mulatta; Male; Mice; Mice, Inbred Strains; Rats; Species Specificity; Time Factors
PubMed: 816458
DOI: No ID Found -
Biochimica Et Biophysica Acta Jul 1960
Topics: Dactinomycin; Humans
PubMed: 13756239
DOI: 10.1016/0006-3002(60)90769-1 -
Biochimica Et Biophysica Acta Jul 2001Actinomycin D is one of the most widely studied anticancer antibiotic that binds to both double-stranded and single-stranded DNA, and this binding greatly enhances the...
Actinomycin D is one of the most widely studied anticancer antibiotic that binds to both double-stranded and single-stranded DNA, and this binding greatly enhances the DNA photosensitization. By use of electron paramagnetic resonance spin trapping techniques, both superoxide radical anion and the radical anion of actinomycin D were identified as important intermediates in the photodynamic process. A mechanism of electron transfer from a DNA base to excited actinomycin D was proposed. These novel findings may shed new light on future application of this drug in photodynamic therapy or cleavage of DNA in unique and controllable ways.
Topics: Antibiotics, Antineoplastic; DNA; Dactinomycin; Electron Spin Resonance Spectroscopy; Electron Transport; Humans; Photochemotherapy
PubMed: 11420136
DOI: 10.1016/s0304-4165(01)00152-0 -
Journal of Molecular Graphics &... Sep 2005The binding of the antitumoral drug actinomycin D to single- and double-stranded DNA was investigated using molecular modeling in the frame of MM+ molecular mechanics... (Comparative Study)
Comparative Study
The binding of the antitumoral drug actinomycin D to single- and double-stranded DNA was investigated using molecular modeling in the frame of MM+ molecular mechanics and AM1 semi-empirical method. Two other programs, especially conceived to analyze hydrogen-bonding patterns in biological macromolecules, HBexplore, based on geometrical criteria and SHB_interactions, based on quantum-chemical criteria (Mulliken overlap populations), were also used. The results account for the non-cooperative intercalative binding process previously investigated, and outline the contribution of specific hydrogen bonding as well as CH...O(N) and other atom-atom intermolecular interactions to the stabilization of the actinomycin D-DNA complexes. They also support the hemi-intercalation model proposed in literature for the actinomycin D-ssDNA complex.
Topics: DNA; DNA, Z-Form; Dactinomycin; Hydrogen Bonding; Models, Chemical; Models, Molecular; Nucleic Acid Conformation; Quantum Theory
PubMed: 15936964
DOI: 10.1016/j.jmgm.2005.03.004