1D and 2D 1H NMR studies on bisantrene complexes with short DNA oligomers.

Abstract

The binding of bisantrene to four DNA tetramers, d(CGCG)2, d(GCGC)2, d(CATG)2, and d(GTAC)2, was investigated by 1D and 2D NMR spectroscopy. Bisantrene is a well known anticancer drug and has been used clinically for years. DNA is believed to be one of its cellular targets. Results from both 1D and 2D 1H NMR are in agreement with an intercalation binding mode of bisantrene with the four DNA tetramers in this study. The results further indicate that a threading intercalation binding mode, in which one bisantrene side chain is in the minor groove and the other in the major groove of DNA, is preferred. The NMR results also suggest that bisantrene prefers binding at pyrimidine-(3',5')-purine intercalation sequences rather than at purine-(3',5')-pyrimidine sequences. The intramolecular and intermolecular NOE contacts of bisantrene-DNA tetramer complexes indicate that a C2'-endo uniform sugar pucker, rather than a mixed sugar conformation, is preferred by the intercalation site of both the 5'-(TA)-3' and the 5'-(CG)-3' binding steps.