STRUCTURE OF COMPLEXES OF DISTAMYCIN TYPE ANTIBIOTICS AND ACTINOMYCIN-D WITH DNA - NEW DATA ON LOCALIZATION OF THESE ANTIBIOTICS WITHIN DNA NARROW GROOVE

  • 1 January 1975
    • journal article
    • research article
    • Vol. 9  (1) , 19-27
Abstract
The antibiotics antinomycin D (AM), netropsin (Nt), distamycin A (DM) and the propyl analog of distamycin A (pDM) when complexed with DNA are located within the narrow groove of DNA. A comparative investigation of the 3H-dimethyl sulfate methylation extent of free calf thymus DNA and its complexes with AM, Nt, DM and pDM reveals that upon DNA saturation these antibiotics decrease the methylation level of the narrow groove (AM by 30%, pDM by 50%, DM by 65% and Nt by 70%). In the triple complex of DNA + AM + DM the methylation level of the narrow groove drops by 80%. The large groove is not shielded by these antibiotics. The methylation level of the large groove decreases by 50% for T6 phage DNA due to the presence of glucosyl residues linked to 5-hydroxymethylcytosine within the large groove. The binding of AM to DNA saturated with Nt or with the analog of distamycin A (DM2) containing the 2 N-methylpyrrole residues was investigated by spectrophotometry. The apparent number of binding sites for AM in these 2 complexes is about half as much as observed for free DNA while the saturation level of the binding decreased only about 20%. This proves simultaneous presence of AM and Nt (DM2) within the narrow groove of DNA.

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