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January 1, 1974Proceedings of the National Academy of SciencesOpen Access

Inhibition of Three Nucleotide Polymerases by Rifamycin Derivatives

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Population

E. coli DNA-dependent DNA polymerase, E. coli DNA-dependent RNA polymerase, and viral RNA-instructed DNA…

Design

Preclinical

Authors

FTFrances M. ThompsonTexas Woman's UniversityATAllan N. TischlerLawrence Berkeley National LaboratoryJAJesse W. AdamsNational Institutes of Health

Discussion

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Implication

It is possible to design rifamycin derivatives that can distinguish between viral RNA-instructed DNA polymerase and other nucleotide polymerases, with higher molecular weight rifazone derivatives showing increased specificity.

Structured PICO

P
Population
E. coli DNA-dependent DNA polymerase (DDP), E. coli DNA-dependent RNA polymerase (DRP), and viral RNA-instructed DNA polymerase (RDP) from murine leukemia virus (MLV)-transformed UC1-B cells
I
Intervention
Rifamycin derivatives (14 derivatives tested, including DMB, Octyloxime, Rifamazine, Dirifampin, RC-7, RC-11, RC-13, RC-16, R-42, R-52, R-62, R-82, Rifampicin, RMI)
O
Outcome
Inhibition constant (KI), defined as the molar concentration of the rifamycin derivative yielding a 50% inhibition of enzyme activitysurrogate

It is possible to design rifamycin derivatives that can distinguish between viral RNA-instructed DNA polymerase and other nucleotide polymerases, with higher molecular weight rifazone derivatives showing increased specificity.

Limitations

  • Specificity measurements are minimum values because DDP is more highly purified than RDP, and other proteins in the RDP extract may bind the derivatives.

Cite This Study

Thompson et al. (1974) studied this question.

synapsesocial.com/papers/6a89bb5cd89205768aeb4628https://doi.org/10.1073/pnas.71.1.107
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Also Consider

Synapse has enriched 2 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1An RNA-Dependent DNA Polymerase in Virions of Rous Sarcoma Virus1970 · 94 citations
  2. 2Rifamycin Antibiotics: Inhibitors of Rauscher Murine Leukemia Virus Reverse Transcriptase and of Purified DNA Polymerases From Human Normal and Leukemic Lymphoblasts1972 · 67 citations