Proposed structure of the anthramycin–DNA adduct

Hurley, Laurence H.; Petrusek, R.

doi:10.1038/282529a0

Cited by 125 publications

(73 citation statements)

References 11 publications

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“…Since most 2-amino groups of guanine are exposed to the narrow groove of DNA, neothramycin may be bound within the minor groove of the double helix. This is in accord with the reports by GLAUBIGER et ala) and by HURLEY et al 19,20). HURLEY8) has assumed that the interaction of pyrrolo(1,4)benzodiazepine antibiotics with DNA occurs in at least two steps : the first being a non-covalent type of interaction and the second covalent attachment : …”

Section: Fsupporting

confidence: 90%

Fluorospectrometric studies on neothramycin and its reaction with DNA.

et al. 1981

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Section: Fsupporting

confidence: 90%

Fluorospectrometric studies on neothramycin and its reaction with DNA.

et al. 1981

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“…The initial neotetrazolium reduction rate was measured at 500 nm and 25°C. SOD was added at a concentration of 5 (5,6,12,13,20), this moiety in dnacin B1 might also be involved in its preferential binding to guanine residues in DNA. In thermal denaturation studies, dnacin B1-treated DNA with a high G+C content ( Fig.…”

mentioning

confidence: 99%

Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties

Tanida¹,

Hasegawa²,

Yoneda³

1982

Antimicrob Agents Chemother

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Dnacin B1 preferentially inhibited the incorporation of [3H]thymidine into acidinsoluble fractions in Escherichia coli. At a sublethal concentration, dnacin B1 caused filamentous growth in E. coli and induced prophage X. The antibiotic also showed potent bactericidal activity against repair-deficient E. coli strains, such as recA, recB, and polA strains. In in vitro studies, dnacin B1 raised the melting temperatures of various double-stranded DNAs. In addition, the antibiotic showed DNA-cleaving activity against PM2 DNA in the presence of reducing agents, and the activity was suppressed by scavengers for oxygen free radicals and an iron-specific chelator, desferrioxamine E. The stimulation of the generation of superoxide radical by dnacin B1 was confirmed by measuring the reduction of neotetrazolium. Therefore, it can be presumed that the primary cellular target of dnacin B1 is DNA in susceptible cells, and the autooxidation of DNA-bound dnacin B1 causes the generation of oxygen-free radicals that result in the damage of DNA and the inhibition of its synthesis.

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“…All three groups of antibiotics contain a carbinolamine functionality. In the case of pyrrolo(1,4)benzodiazepine antibiotics, the carbinolamine functionality has been directly implicated in the binding site of these antibiotics to DNA (7). Naphthyridinomycin also contains a carbinolamine at a position analogous to the position of the carbinolamine in saframycin S. Based on results with other carbinolamine antibiotics, it would be reasonable to speculate that the carbinolamine of naphthyridinomycin is involved in the binding of this antibiotic to DNA.…”

Section: Dna the Reactivity Of [3h]naphthyridinomycinmentioning

confidence: 99%

Naphthyridinomycin, a DNA-reactive antibiotic

Zmijewski¹,

Miller-Hatch²,

Goebel³

1982

Antimicrob Agents Chemother

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Naphthyridinomycin is a novel quinone antibiotic that is produced in liquid shake cultures by Streptomyces lusitanus. Fermentation studies have shown that this antibiotic is produced maximally after 96 h of cell growth. L-[methyl-3H]methionine efficiently labels naphthyridinomycin when it is added to a fermentation mixture 24 h before culture is harvested. Unlabeled and radioactively labeled naphthyridinomycin were used to determine the mechanism of action of this unique antibiotic. Naphthyridinomycin inhibited bacterial growth primarily by inhibiting DNA synthesis. The structural similarity between naphthyridinomycin and the saframycins suggested that naphthyridinomycin might inhibit DNA synthesis by binding to the template. In vitro studies with radiolabeled naphthyridinomycin indicated that this antibiotic does specifically bind to calf thymus DNA. The binding reaction was enhanced by adding sulfhydryl-containing compounds; dithiothreitol was the best activating agent. DNA-naphthyridinomycin complexes were a poor substrate for enzymes that catalyze DNA-directed DNA and RNA syntheses. These results showed that naphthyridinomycin is similar to the saframycins in its reactivity toward DNA and suggested that the mechanism by which naphthyridinomycin inhibits DNA synthesis is through its ability to bind specifically to the DNA template of the cell.

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Proposed structure of the anthramycin–DNA adduct

Cited by 125 publications

References 11 publications

Fluorospectrometric studies on neothramycin and its reaction with DNA.

Fluorospectrometric studies on neothramycin and its reaction with DNA.

Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties

Naphthyridinomycin, a DNA-reactive antibiotic

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