7-Amino-actinomycin D complexes with deoxynucleotides as models for the binding of the drug to DNA
✍ Scribed by Yu-Chih Chen Chiao; K. Gurudath Rao; John W. Hook III; Thomas R. Krugh; Sisir K. Sengupta
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1979
- Tongue
- English
- Weight
- 798 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0006-3525
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Fluorescence, CD, absorption, and ^1^H‐nmr studies are reported for complexes of 7‐amino‐actinomycin D with deoxydinucleotides, deoxytetranucleotides, and poly(__d__G‐__d__C)· poly(__d__G‐__d__C). The optical spectra for the 7‐amino‐actinomycin D complex with p__d__G‐__d__C, p__d__G‐__d__C‐__d__G‐__d__C and p__d__C‐__d__G‐__d__C‐__d__G are similar in shape to the 7‐amino‐actinomycin D complex with either DNA or poly(__d__G‐__d__C). The changes in the ^1^H chemical shifts of the 7‐amino‐actinomycin D and the p__d__G‐__d__C resonances that accompany complex formation show that 7‐amino‐actinomycin D forms a minature intercalated complex with two p__d__G‐__d__C molecules. The magnitudes of the induced chemical shifts for the 7‐amino‐actinomycin D complex formation with p__d__G‐__d__C are similar to, but slightly different from, the induced chemical shifts which are obtained when actinomycin D forms a minature intercalated complex with two p__d__G‐d__C molecules. The p__dN‐__d__G 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 [K~D~(6°C) = 4.4 × 10^3^M^−1^], as compared to actinomycin D [K~D~(6°C) = 1.7 × 10^3^M^−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(__d__G‐__d__C)·poly(__d__G‐__d__C), and poly(__d__A‐__d__C)·poly(__d__G‐__d__T), results in an enhancement of the relative fluorescence intensity and a shift in both the absorbance and corrected emission spectra.