Solution studies on the complex of 4′-epiadriamycin-d-(CGATCG)2 followed by time-resolved fluorescence measurement, diffusion ordered spectroscopy and restrained molecular dynamics simulations

4′-Epiadriamycin is a better-tolerated anthracycline drug, due to lesser cardiotoxicity. We report here a study of the 2:1 complex of 4′-epiadriamycin-d-(CGATCG)2 by proton Nuclear Magnetic Resonance Spectroscopy which show the absence of sequential connectivities between C1pG2 and C5pG6 base pair steps and presence of intermolecular cross peaks of the drug and DNA. Our studies establish the role of 9OH, NH3+, 7O, 4OCH3 groups in binding to DNA. Time-resolved fluorescence measurement and diffusion ordered spectroscopic studies reveal the formation of complex. The nonspecific interactions as well as those essential for biological activity are discussed along with its medicinal importance.

Binding of 4′-epiadriamycin, an anthracycline anticancer drug, with d-(CGATCG)2 hexamer sequence to understand the drug–DNA interaction which is the primary step to comprehend the potent activity and low toxicity of this drug.Figure optionsDownload as PowerPoint slide