Anthramycin DNA complex

The geometry of the anthramycin-DNA complex is of interest because of the small size of anthramycin, the firmness of the binding and the apparent base of interest for comparison with previously studied complexes of small molecules with DNA, partially Actinomycin-D. 

Table 1 shows the viscosity and sedimentation data obtained for anthramycin DNA complexes using DNA of various molecular weights. The molecular weight of DNA used in these measurements was varied because of the observation of Muller and Crothers on Actinomycin-D complexes which indicated that the hydrodynamic properties of the com-... 

The combination of the hydrodynamic properties of anthramycin-DNA complexes together with the Electric Dichroism measurements permit us to conclude that anthramycin is bound to DNA in a sterically specific manner, that the complex is stable at low ionic strength, and that the anthramycin molecule is not intercalated between base pairs, the anthramycin chromophore being oriented at an angle of approximately 36° with respect to the helix axis. 

Abstract Aspects of the geometry of complexes between antineoplastic agents and DNA can be determined using hydrodynamic measurements and using the technique of Electric Dichroism. Data is presented for two compounds, anthramycin and ellipticine, which shows that ellipticine binds to DNA by intercalation while anthramycin does not, the chromophore portion of the anthramycin molecule being inclined at an angle of approximately 36 with respect to the helix axis. 

Anthramycin-11 methyl ether (11-Me-O-anthramycin) was obtained from Hoffman-LaRoche (Lot F-60). Stock solutions in methanol or dimethylformamide were stored at -15°C. Concentrations were based on a molar extinction coefficient of 35 000 at 333 nm in aqueous solution at pH 7. Complexes of anthramycin and DNA were prepared by adding a small amount of a concentrated anthramycin solution to a solution of DNA in 0.14f PO4 buffer pH 6.1 and permitting the reaction to continue for 8 hr at 23 °C. The concentration of DNA was determined using a molar extinction coefficient of 6700 per mole nucleotide residue at 260 nm. 

Anthramycin has previously been shown to react preferentially with helical, or native, DNA [6]. The reactive site appears to involve deoxyguanylic acid residues, since only guanine-containing deoxypolynucleotides are reactive [7]. The complex formed is extremely stable and resists dissociation by dialysis, gel filtration, alcohol precipitation, sodium lauryl sulfate and silver ion. In addition, separation of DNA strands by alkali de-naturation fails to dissociate bound anthramycin [8]. 

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