Antibiotic U-24,544 is a new agent isolated from the culture broth of a streptomycete strain. The antibiotic inhibits a variety of gram-positive and gram-negative bacteria in vitro, but is ...ineffective in treatment of experimental bacterial infections in mice. It is fairly cytotoxic in mammalian cell cultures and remarkably nontoxic in mice.
Mixtures of DNA with the three antibiotics zorbamycin, phleomycin or bleomycin were analyzed by UV and circular dichroism measurements. The results indicate that a physical interaction between ...isolated DNA and each of the three antibiotics occurs and that these antibiotics definitely bind to DNA.
The amphiphilic novenamines described in this report have been shown previously to be specific inhibitors of human immunodeficiency virus type 1 reverse transcriptase-associated ribonuclease, which ...they inhibit when they are in the micellar state but not when they are monomeric. These compounds also inhibit the bacterial enzyme DNA gyrase, which is essential for DNA replication. Hence, the present studies were initiated to determine whether the molecular species inhibiting the gyrase reaction was the monomeric or the micellar form. For this purpose, the rate of DNA replication was measured in a toluenized
Escherichia coli cell system in the presence of increasing concentrations of novenamines. The resulting concentration-response curves proved anomalous, suggesting the involvement of micelles or some other, noncovalently aggregated forms of the inhibitors. The results were analyzed in terms of a variety of kinetic schemes and were found to be most consistent with the model where novenamines inhibit replicative DNA synthesis predominantly as cooperative dimers and, to a lesser extent, as monomers, but not as highly aggregated micelles. Based on this analysis and the knowledge that novobiocin and all novenamine-containing analogs are powerful gyrase inhibitors, we conclude that the target of the cooperative, dimeric inhibition is the gyrase, whereas the monomers of the novenamines inhibit another enzyme species involved in the bacterial DNA replication process.
Chlorobiocic acid and 3-(carbobenzoxyamino)-4, 7-dmydroxy-8-methylcoumarin were identified as two new inhibitors of Micrococcus luteus DNA gyrase. Both compounds possess weak antibacterial activity ...against whole M. luteus cells which indicates that they probably lack efficient transport functions to penetrate the cell envelope.
The antibiotic steffimycin B binds to double-stranded DNA as evidenced by difference spectroscopy and an increase of the thermal stability of DNA in the presence of the antibiotic. Salmon sperm ...DNA-steffimycin B complexes show a drastic decrease in template activity for Escherichia coli DNA polymerase I but not for DNA-idrected RNA polymerase. The differences in template properties of polyd(A-T) and poly (dG) - poly(dC)-antibiotic complexes,respectively, for DNA polymerase I and RNA polymerase suggest that the antibiotic interacts primarily with adenine or thymine bases or both in double-stranded DNA.
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