Studies on the interaction of adriamycin with d-(TGATCA)2 by proton nuclear magnetic resonance spectroscopy, time-resolved fluorescence measurement, diffusion ordered spectroscopy followed by structural refinement using restrained molecular dynamics appro

Adriamycin is one of the most potent anticancer anthracycline drug having aromatic chromophore and an amino sugar moiety. We report here the solution structure of 2:1 adriamycin–d-(TGATCA)2 complex which has been determined using restrained molecular dynamics. Sequential NOE (nuclear Overhauser effect) connectivities between T1pG2 and C5pA6 steps are not observed on the intercalation of the drug chromophore at these base pair steps. Presence of several other intermolecular NOEs, that is, T1CH37H, T1CH310eqH and C5H64OCH3 corroborate the same. The specificity of interaction arises from the O-glycosidic dihedral bond C7O7C1′C2′ (133°), positioning of NH3+ moiety in minor groove, conformation of ring A and daunosamine sugar. Besides this, diffusion ordered spectroscopy (DOSY) studies prove the formation of complex and time-resolved fluorescence measurement studies provide evidence for shortening of decay time on complex formation. The nonspecific interactions as well as those essential for molecular basis of drug action are discussed along with the specificity of interactions in the drug–DNA complex, which is responsible for the anticancer action of the drug.