TEMPLATE SPECIFICITY OF DNA-BINDING BY NOGALAMYCIN AND ITS ANALOGS UTILIZING COMPETITIVE FLUORESCENCE POLARIZATION

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2235-2240
Abstract
Nogalamycin, an anthracycline antibiotic [similar to many antitumor agents] interacts with DNA. This interaction is measured by a competitive fluorescence polarization assay in which nogalamycin displaces acridine orange. The amount of acridine orange displaced is dependent upon the concentration and DNA-binding capability of the drug. The relative DNA-binding capacities of several nogalamycin analogs are also determined by this method. A comparison of these results with circular dichroism and thermal denaturation yields a positive correlation. The base-pair specificities of these compounds are also evaluated by competitive fluorescence polarization using DNA of differing base composition. Apparently, compounds containing the nogalose moiety generally prefer adenine and thymine. Some of the 7-O-alkyl analogs appear to interact similarly with DNA of differing base composition, and others show a preference for DNA with high guanine and cytosine content. Specificities obtained with this method are compared with DNA thermal denaturation and polymerase inhibition studies. The potential value of this relatively new competitive method for the study of DNA-reactive antitumor compounds is discussed.