7-Amino-actinomycin D complexes with deoxynucleotides as models for the binding of the drug to DNA.

Abstract

AbstractFluorescence, CD, absorption, and 1H‐nmr studies are reported for complexes of 7‐amino‐actinomycin D with deoxydinucleotides, deoxytetranucleotides, and poly(dG‐dC)· poly(dG‐dC). The optical spectra for the 7‐amino‐actinomycin D complex with pdG‐dC, pdG‐dC‐dG‐dC and pdC‐dG‐dC‐dG are similar in shape to the 7‐amino‐actinomycin D complex with either DNA or poly(dG‐dC). The changes in the 1H chemical shifts of the 7‐amino‐actinomycin D and the pdG‐dC resonances that accompany complex formation show that 7‐amino‐actinomycin D forms a minature intercalated complex with two pdG‐dC molecules. The magnitudes of the induced chemical shifts for the 7‐amino‐actinomycin D complex formation with pdG‐dC are similar to, but slightly different from, the induced chemical shifts which are obtained when actinomycin D forms a minature intercalated complex with two pdG‐dC molecules. The pdN‐dG dinucleotides (N = C, A, or T) form stacked complexes with 7‐amino‐actinomycin D. The presence of the 7‐amino‐group results in a larger dimerization constant (in aqueous solution) for 7‐amino‐actinomycin D [KD(6°C) = 4.4 × 103M−1], as compared to actinomycin D [KD(6°C) = 1.7 × 103M−1]; the chemical shifts which accompany dimer formation indicate that the chromophores stack in an inverted manner. Intercalation of 7‐amino‐actinomycin D into minature double helices, as well as into calf thymus DNA, poly(dG‐dC)·poly(dG‐dC), and poly(dA‐dC)·poly(dG‐dT), results in an enhancement of the relative fluorescence intensity and a shift in both the absorbance and corrected emission spectra.