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Annals of the New York Academy of... Oct 1960
Topics: Dactinomycin
PubMed: 13790233
DOI: 10.1111/j.1749-6632.1960.tb20156.x -
Biochemistry Jun 1993The influences of base sequence on the thermodynamic properties associated with the interaction of actinomycin D with DNA are examined. It has been previously...
The influences of base sequence on the thermodynamic properties associated with the interaction of actinomycin D with DNA are examined. It has been previously established that GpC steps of double-helical DNAs are highly preferred binding sites for actinomycin D. In this study, a series of oligonucleotides was designed and synthesized to probe the effects of flanking base sequence (adjacent to the GpC step) and novel non-GpC binding sites on the binding of actinomycin D. The use of these oligonucleotides provides a direct method for quantitating sequence specificities and actinomycin D binding energetics. Effects of different 5' and 3' flanking nucleotides on the interactions of actinomycin with the core GpC binding sites were examined using UV-visible spectrophotometric methods, and changes in binding energetics were quantitated. These studies demonstrate strong actinomycin D binding affinities to both classical GpC and an atypical non-GpC site. Enthalpy and entropy components of the DNA binding energetics for the GpC binding sites are compared and correlated with those determined for actinomycin D binding to the high-affinity non-GpC site of an 11-mer containing TGGGT as the central sequence. This TGGGT site, first suggested to be a high-affinity sequence in our earlier photoaffinity labeling studies, exhibits binding of actinomycin D comparable in strength to that of traditional actinomycin D binding sites (i.e., GpC steps). From these studies, the overall affinity and specific thermodynamic contributions (delta H degree, delta S degree) to binding of actinomycin D are demonstrated to be highly influenced both by the sequence at the intercalation site and by neighboring bases which flank the intercalation site.
Topics: Amino Acid Sequence; Base Sequence; Binding Sites; DNA; Dactinomycin; Molecular Sequence Data; Structure-Activity Relationship; Thermodynamics
PubMed: 8504108
DOI: 10.1021/bi00073a022 -
Cancer Research Sep 1976Unilamellar lipid vesicles have been used as a carrier vehicle to enhance the uptake of actinomycin D into an actinomycin D-resistant Chinese hamster tumor cell line...
Unilamellar lipid vesicles have been used as a carrier vehicle to enhance the uptake of actinomycin D into an actinomycin D-resistant Chinese hamster tumor cell line (DC-3F/ADX). The DC-3F/ADX cell line is resistant to actinomycin D as a result of its decreased capacity to transport actinomycin D across the plasma membrane and is able to grow in the presence of concentrations of actinomycin D that are cytotoxic for the sensitive parent cell line (DC-3F). Incubation of resistant DC-3F/ADX cells with actinomycin D-containing vesicles produced a 5-fold increase in intracellular drug concentration over that achieved by exposure to identical concentrations of the drug added to the culture medium. Vesicle-mediated uptake of actinomycin D into resistant cells produced inhibition of cellular RNA synthesis and cell growth at actinomycin D concentrations that had no inhibitory effect when added as free drug in the culture medium. Dose-response measurements established that direct introduction of actinomycin D into resistant cells by means of lipid vesicles resulted in a 200-fold reduction in the concentration of actinomycin D required to inhibit cellular RNA synthesis and a 120-fold reduction in the dose of actinomycin D required to produce a 50% inhibition of cell growth. These results lend strong support to the hypothesis that cellular resistant to actinomycin D is due to a lower capacity to take up actinomycin D as a result of a reduction in the permeability of the cellular plasma membrane to this drug. The potential value of lipid vesicles for introducing other classes of drugs into cultured cells and their possible use in chemotherapy are also discussed.
Topics: Animals; Cell Division; Cell Line; Cell Membrane; Dactinomycin; Dose-Response Relationship, Drug; Drug Resistance; Lipids; Neoplasms, Experimental; Pharmaceutical Vehicles; RNA, Neoplasm
PubMed: 975068
DOI: No ID Found -
Journal of Medicinal Chemistry Nov 19752-Deamino- and N2-(gamma-hydroxypropyl)actinomycin D were synthesized by modification of the parent actinomycin D molecule at the 2 position of the phenoxazinone moiety....
2-Deamino- and N2-(gamma-hydroxypropyl)actinomycin D were synthesized by modification of the parent actinomycin D molecule at the 2 position of the phenoxazinone moiety. The common intermediate was 2-deamino-2-chloroactinomycin D. Catalytic hydrogenation of this material afforded the 2-deamino derivative while treatment with gamma-hydroxypropylamine yielded the N2-(gamma-hydroxypropyl) derivative. These 2-substituted actinomycin D derivatives were less potent in microbiological assays than the parent compound. Evaluation of activity in vivo against three murine tumor systems indicated that optimal dose levels of 2-deaminoactinomydin D were 50 times greater than toxic dose levels of actinomycin D. N2-(gamma-hydroxyporpyl)actinomycin D exhibited antitumor activity similar to the parent compound.
Topics: 1-Propanol; Animals; Antineoplastic Agents; Bacillus subtilis; Dactinomycin; Deamination; Leukemia L1210; Leukemia, Experimental; Male; Melanoma; Mice; Microbial Sensitivity Tests; Neoplasms, Experimental; Sarcina; Spectrophotometry; Staphylococcus aureus
PubMed: 809581
DOI: 10.1021/jm00245a010 -
Cancer Research Dec 1977Sublines of P388 leukemia resistant to Adriamycin and daunorubicin were cross-resistant to actinomycin D in vivo and in vitro. The Adriamycin-resistant cell line was...
Sublines of P388 leukemia resistant to Adriamycin and daunorubicin were cross-resistant to actinomycin D in vivo and in vitro. The Adriamycin-resistant cell line was 1000-fold resistant to actinomycin D on 1-hr exposure in vitro and 370-fold resistant when exposed to the drug for 16 hr. The immediate binding of radioactive actinomycin D to sensitive and resistant cells was similar, and the uptake of the drug by the resistant cells was only about 27% less than the rate of uptake by sensitive cells. There was a dramatic difference in efflux of drug from sensitive and resistant sublines. Equivalent cytotoxicity of actinomycin D for the sensitive and resistant sublines was obtained at concentrations of the drug that resulted in approximately equivalent levels of net retention of actinomycin D (retained drug minus background levels of immediate binding of the drug to the cells). Incubation of cells in the presence of actinomycin D plus either Tween 80 or acridine orange incresed the rate of uptake and the percentage of actinomycin D retained by the resistant cells on short-term assays but did not reverse the resistance. It is concluded that these tumors must retain appreciable concentrations of actinomycin D for several hr in order to be killed. The anthracycline-resistant sublines are cross-resistant to actinomycin D by virtue of their inability to retain the drug.
Topics: Acridines; Animals; Cell Line; Cell Survival; Dactinomycin; Daunorubicin; Doxorubicin; Drug Resistance; Leukemia, Experimental; Liposomes; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Polysorbates
PubMed: 922743
DOI: No ID Found -
Pediatrics Oct 1959
Topics: Child; Dactinomycin; Humans; Infant; Neoplasms
PubMed: 13836792
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Mar 1976A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After... (Comparative Study)
Comparative Study
A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.
Topics: Amino Acids; Bacteria; Chemical Phenomena; Chemistry; Dactinomycin; Fermentation; Micromonospora
PubMed: 56917
DOI: 10.1128/AAC.9.3.465 -
Journal of Bacteriology May 1969Growth of 20 of 22 strains of gliding bacteria (including fruiting myxobacteria) was inhibited by relatively low concentrations of actinomycin D.
Growth of 20 of 22 strains of gliding bacteria (including fruiting myxobacteria) was inhibited by relatively low concentrations of actinomycin D.
Topics: Bacteria; Dactinomycin; Drug Resistance, Microbial
PubMed: 5784235
DOI: 10.1128/jb.98.2.851-852.1969 -
Applied Microbiology Aug 1968
Topics: Chromatography, Paper; Dactinomycin; Lactones; Streptomyces; Tritium
PubMed: 4175382
DOI: 10.1128/am.16.8.1258-.1968 -
Experientia Nov 1963
Topics: Animals; DNA; Dactinomycin; Echinodermata; Embryo, Mammalian; Embryo, Nonmammalian; Lithium; Metabolism; Morphogenesis; Paracentrotus; Pharmacology; RNA; Research; Sea Urchins; Thymidine; Zinc
PubMed: 14101510
DOI: 10.1007/BF02150995