Affinity of anticancer drug,daunomycin,to core histones in solution:comparison of free and cross-lin

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:LJC21102309
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Aim:The interaction of anthracycline anticancer drugs with chromatin,nucleo-somes and histone H1 has been extensively studied.In the present study,for thefirst time,we have investigated the binding of anthracycline antibiotic,daunomycin,to free and cross-linked thymus core histories (CL-core) in solution and in theabsence of DNA.Methods:Fluorescence,UV/Vis spectroscopy and equilibriumdialysis techniques were used.Results:The UV spectroscopy results show thatdaunomycin induces hypochromicity in the absorption spectra of the core histones.Fluorescence emission intensity is decreased upon daunomycin binding and theprocess is concentration dependent.The equilibrium dialysis shows that the bind-ing is positive cooperative with the binding sites as Scatchard plot and Hill Coef-ficient confirm it.Conclusion:The results suggest that daunomycin shows muchhigher affinity to core histones free in solution than to CL-core,implying that thebinding 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 asin tumor cells,rather than to their compact structure seen in normal chromatin. Aim: The interaction of anthracycline anticancer drugs with chromatin, nucleo-somes and histone H1 has been extensively studied.In the present study, for thefirst time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histories (CL-core) in solution and in the presence of DNA. Methods: Fluorescence, UV / Vis spectroscopy and equilibriumdialysis 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 bind-ing is positive cooperative with the binding sites as Scatchard plot and Hill Coef-ficient confirm it.Conclusion: The results suggest that daunomycin shows muchhigher affinity to core histones free in solution than to CL-core, implying that the binding is most likely due to the accessibility of these pr oteins to the environment. It is suggested that daunomycin binds strongly to open state of histones, such as as in tumor cells, rather than to compact structure seen in normal chromatin.
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