Abstract
Aim:
The interaction of anthracycline anticancer drugs with chromatin, nucleosomes and histone H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histones (CL-core) in solution and in the absence of DNA.
Methods:
Fluorescence, UV/Vis spectroscopy and equilibrium dialysis techniques were used.
Results:
The UV spectroscopy results show that daunomycin induces hypochromicity in the absorption spectra of the core histones. Fluorescence emission intensity is decreased upon daunomycin binding and the process is concentration dependent. The equilibrium dialysis shows that the binding is positive cooperative with the binding sites as Scatchard plot and Hill Coefficient confirm it.
Conclusion:
The results suggest that daunomycin shows much higher affinity to core histones free in solution than to CL-core, implying that the binding is most likely due to the accessibility of these proteins to the environment. It is suggested that daunomycin binds strongly to open state of histones, such as in tumor cells, rather than to their compact structure seen in normal chromatin.
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Project supported by a grant from the research office of the University of Tehran to Azra Rabbani (No 512-1-217).
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Rabbani, A., Abdosamadi, S. & Sari-saraf, N. Affinity of anticancer drug, daunomycin, to core histones in solution: comparison of free and cross—linked proteins. Acta Pharmacol Sin 28, 731–737 (2007). https://doi.org/10.1111/j.1745-7254.2007.00542.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00542.x