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Journal of Reproduction and Fertility Nov 1976Treatment of preimplantation mouse embryos in vitro with 10(-3) to 10(-1) mug actinomycin D/ml for 2 hr showed that (i) postimplantation development in vitro was...
Treatment of preimplantation mouse embryos in vitro with 10(-3) to 10(-1) mug actinomycin D/ml for 2 hr showed that (i) postimplantation development in vitro was inhibited most when embryos were treated at the morula stage and (ii) after the morula stage actinomycin D inhibited trophoblast outgrowth less than inner cell mass development.
Topics: Animals; Blastocyst; Dactinomycin; Embryo, Mammalian; Female; In Vitro Techniques; Mice; Superovulation; Trophoblasts
PubMed: 1033287
DOI: 10.1530/jrf.0.0480443 -
Nucleic Acids Research Dec 1994The antitumour antibiotic actinomycin D normally binds to DNA by intercalation at sequences containing the CpG step, but in the presence of daunomycin it has been...
The antitumour antibiotic actinomycin D normally binds to DNA by intercalation at sequences containing the CpG step, but in the presence of daunomycin it has been reported to interact with poly(dA-dT). This observation has neither been confirmed nor explained. Here we have used a photoreactive 7-azido derivative of actinomycin to study the effect of daunomycin on its binding to three DNA fragments. Daunomycin did indeed alter the binding of actinomycin to the DNA, such that the antibiotic was displaced from its primary GpC sites onto secondary sites in the DNA, though not to AT regions especially. These findings suggest a possible scientific explanation for the increased toxicity seen during combination chemotherapy with these two drugs.
Topics: Base Sequence; DNA; Dactinomycin; Daunorubicin; Dinucleoside Phosphates; Molecular Sequence Data; Photolysis; Poly dA-dT
PubMed: 7816612
DOI: 10.1093/nar/22.24.5241 -
The Journal of Biological Chemistry Mar 1961
Topics: Dactinomycin; Enzymes; Oxazines; Pigments, Biological
PubMed: 13784113
DOI: No ID Found -
Cancer Letters Sep 2008Leu5AMD ([D-Val2, L-MeLeu5]2 AMD) is a novel actinomycin D (AMD) analog, in which both N-methylvalines were replaced by N-methylleucines. In the present study, an...
Leu5AMD ([D-Val2, L-MeLeu5]2 AMD) is a novel actinomycin D (AMD) analog, in which both N-methylvalines were replaced by N-methylleucines. In the present study, an attempt has been made to investigate the effects of Leu5AMD on the proliferation of human gastric carcinoma cell line SGC-7901. The results showed that Leu5AMD inhibited the proliferation and induces apoptosis in SGC-7901 cells in a dose-dependent manner. Apoptosis induced by Leu5AMD was further confirmed by annexin V-FITC/PI dual staining assay. After treatment with Leu5AMD, the loss of mitochondrial potential and the decrease of bcl-2 gene expression were observed in apoptotic cells, suggesting that Leu5AMD may be involved in mitochondria and bcl-2 related apoptotic pathway. In addition, the in vivo antitumor effects of Leu5AMD on S-180 bearing mice and the acute toxicity on healthy mice were investigated. Treatment with Leu5AMD markedly suppressed the growth of Sarcoma xenograft. These results suggest that Leu5AMD may be used as a promising chemotherapeutical agent for patients affected by gastric carcinoma and other solid cancer.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dactinomycin; Dose-Response Relationship, Drug; Humans; Membrane Potential, Mitochondrial; Mice; Proto-Oncogene Proteins c-bcl-2; Sarcoma 180; Stomach Neoplasms; Xenograft Model Antitumor Assays
PubMed: 18448241
DOI: 10.1016/j.canlet.2008.03.026 -
Antibiotiki Jan 1981A new actinomycin was isolated from a mixture of actinomycins formed by Actinomyces sp. No. 2, an organism producing auranthin, an actinomycetous antibiotic. The peptide...
A new actinomycin was isolated from a mixture of actinomycins formed by Actinomyces sp. No. 2, an organism producing auranthin, an actinomycetous antibiotic. The peptide chains of the new actinomycin contain such amino acids as threonine, valine, proline and sarcosine in a ratio of 2 : 4 : 2 : 2. N-Methyl-valine characteristic of all actinomycins is replaced in position 5 of both pentapeptide chains of the new actinomycin by valine. The new actinomycin is actinomycin D undermethylated in position 5 by valine. When the growing culture of Actinomyces olivobrunneus producing actinomycin D was exposed to sulfadimesine, an inhibitor of biological methylation, production of actinomycin D0 (sarcosine replaced by glycine in one of the pentapeptide chains) markedly increased, which indicated impairment of the glycine residue methylation. Still, no impairment of the valine residue methylation in position 5 of the pentapeptide chains was observed an no actinomycin with N-methyl-valine replaced by valine was formed.
Topics: Actinomyces; Amino Acid Sequence; Amino Acids; Dactinomycin; Methylation; Peptides
PubMed: 6163396
DOI: No ID Found -
Journal of Medicinal Chemistry Jul 1978Six-bis-dipeptide analogues of actinomycin D, all containing two threonyl-D-valine side chains, were prepared. Also two bis-tripeptide analogues containing an additional...
Six-bis-dipeptide analogues of actinomycin D, all containing two threonyl-D-valine side chains, were prepared. Also two bis-tripeptide analogues containing an additional proline or oxoproline residue were synthesized. None of the compounds bound to DNA in a manner similar to actinomycin D. This lack of strong intercalative binding emphasizes the importance of the pentapeptidolactone side chains in the binding of actinomycin D to DNA and also highlights the deficiences inherent in using only small nucleotide sequences in investigating drug-DNA binding. None of the analogues tested showed any antitumor activity, although actinocylbis(threonyl-D-valine methyl ester) did show 10% of the antibacterial activity of actinomycin D vs. Bacillus subtilis.
Topics: Animals; Bacillus subtilis; DNA; Dactinomycin; Dipeptides; In Vitro Techniques; Leukemia, Experimental; Mice; Microbial Sensitivity Tests; Oligopeptides
PubMed: 97381
DOI: 10.1021/jm00205a004 -
The Journal of Biological Chemistry Jul 1984Several structural analogs of 4-methyl-3-hydroxyanthranilic acid (4-MHA) that had been established as substrates of the 4-MHA-activating enzyme from Streptomyces...
Several structural analogs of 4-methyl-3-hydroxyanthranilic acid (4-MHA) that had been established as substrates of the 4-MHA-activating enzyme from Streptomyces chrysomallus (Keller, U., Kleinkauf, H., and Zocher, R. (1984) Biochemistry 23, 1479-1484) were fed in short term labeling experiments to cultures of two actinomycin-producing streptomycetes. Besides inhibition of actinomycin synthesis, the addition of 4-methyl-3-hydroxybenzoic acid, 3-hydroxybenzoic acid, 4-aminobenzoic acid, or 4-methyl-3-methoxy-benzoic acid induced the formation of novel compounds. The data indicate that these compounds are structural analogs of 4-MHA pentapeptide lactones, which are the most probable precursors of actinomycins (Katz, E. (1967) in Antibiotics II (Gottlieb, D., and Shaw, P. D., eds) pp. 276-341, Springer-Verlag, New York). Since the structural analogs of 4-MHA are missing the o-aminophenol configuration, the corresponding acyl pentapeptide lactones cannot react with each other to give phenoxazines. Therefore, they accumulate and thus become detectable. Feeding cultures with 4-MHA resulted in an inhibition of actinomycin synthesis apparently at the level of acyl pentapeptide lactone synthesis. In such experiments, the formation of pentapeptide lactones, which are most likely derived from 4-MHA pentapeptide lactones, could be detected. The results provide experimental evidence that the biosynthesis of actinomycins proceeds via the 4-MHA-pentapeptide lactones.
Topics: Amino Acids; Carbon Radioisotopes; Dactinomycin; Lactones; Oligopeptides; Streptomyces; Structure-Activity Relationship; ortho-Aminobenzoates
PubMed: 6203903
DOI: No ID Found -
Bioorganic & Medicinal Chemistry May 1996The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our...
The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our search for a novel class of nucleic acid binders. A highly convergent, solid-phase synthetic strategy has been developed for a class of peptide-aryl-peptide conjugates modeled upon natural actinomycins. The features of this method include the use of Fmoc solid-phase peptide synthesis, side-chain to side-chain cyclization on the solid phase, a chemoselective cleavage step and segment condensation. The synthetic scheme is consistent with the requirements for combinatorial synthesis and furthermore, the final segment condensation allows, for the first time, double-combinatorial chemistry to be performed where two combinatorial libraries can be reacted with each other.
Topics: Amino Acids; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; DNA; Dactinomycin; Drug Design; Gas Chromatography-Mass Spectrometry; Intercalating Agents; Magnetic Resonance Spectroscopy; RNA; Spectrophotometry, Ultraviolet
PubMed: 8804535
DOI: 10.1016/0968-0896(96)00065-x -
Canadian Journal of Genetics and... Sep 1969
Topics: Alkylating Agents; Dactinomycin; Ethers, Cyclic; Plants; Recombination, Genetic
PubMed: 5370990
DOI: 10.1139/g69-087 -
The Journal of Antibiotics Feb 1971
Topics: Chromatography, Thin Layer; Dactinomycin; Fermentation; Lactones; Spectrophotometry; Streptomyces; Ultraviolet Rays
PubMed: 4101129
DOI: 10.7164/antibiotics.24.135