Spectroscopic studies of dactinomycin and vinorelbine binding to deoxyribonucleic acid and chromatin
Azra Rabbani-Chadegani1, Saeedeh Keyvani-Ghamsari, Nasrin Zarkar
1Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. rabbani@ibb.ut.ac.ir
Abstract:
Dactinomycin and vinorelbine are anticancer drugs, widely used as chemotherapeutic agents for the treatment of various cancers. This study represents an attempt to compare the effect of these drugs on DNA and soluble chromatin employing UV/vis, fluorescence and circular dichroism spectroscopy techniques. The results demonstrated that the absorbance at 260 and 210 nm was decreased and quenching of drugs with DNA and chromatin chromospheres induced reduction of fluorescence emission intensity. Circular dichroism profiles showed that the binding of drugs induced structural changes in both positive and negative extremes of DNA and chromatin revealing release or displacement of histone proteins from chromatin upon dactinomycin binding whereas vinorelbine preceded the chromatin into compaction. The results suggest that dactinomycin shows higher affinity to DNA compared to chromatin, whereas, vinorelbine recognizes the chromatin structure with higher affinity than free DNA. Also chromatin proteins play a fundamental role in drug-chromatin complex process.


