Substituents on etoposide that interact with human topoisomerase II[alpha] in the binary enzyme-drug complex: contributions to etoposide binding and activity

DNA cleavage assays, saturation transfer difference [super 1]H NMR spectroscopy, and enzyme-drug binding studies were conducted to define interactions between etoposide and human topoisomerase II[alpha]. The results suggest that the binding of etoposide to human topoisomerase II[alpha] is driven by interactions with the A- and B-rings and potentially by stacking interactions with the E-ring.