The anticancer drug–DNA complex: Femtosecond primary dynamics for anthracycline antibiotics function

AUTOR(ES)

Qu, Xiaogang

FONTE

The National Academy of Sciences

RESUMO

The anthracycline–DNA complex, which is a potent agent for cancer chemotherapy, has a unique intercalating molecular structure with preference to the GC bases of DNA, as shown by Rich's group in studies of single-crystal x-ray diffraction. Understanding cytotoxicity and its photoenhancement requires the unraveling of the dynamics under the solution-phase, physiological condition. Here we report our first study of the primary processes of drug function. In a series of experiments involving the drug (daunomycin and adriamycin) in water, the drug–DNA complexes, the complexes with the four nucleotides (dGTP, dATP, dCTP, and dTTP), and the drug-apo riboflavin-binding protein, we show the direct involvement of molecular oxygen and DNA base-drug charge-separation—the rates for the reduction of the drug and dioxygen indicate the crucial role of drug/base/O2 in the efficient and catalytic redox cycling. These dynamical steps, and the subsequent reactions of the superoxide product(s), can account for the photoenhanced function of the drug in cells, and potentially for the cell death.

Documentos Relacionados

• Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG).
• Investigation of DNA dynamics and drug-DNA interaction by steady state fluorescence anisotropy.
• Characterization of the minor groove environment in a drug-DNA complex: bisbenzimide bound to the poly[d(AT)].poly[d(AT)]duplex.
• Enthalpy-entropy compensations in drug-DNA binding studies.
• Femtosecond dynamics of a drug–protein complex: Daunomycin with Apo riboflavin-binding protein