Assessment of the sequence dependency for the binding of 2-aminonaphthyridine to the guanine bulge

We have studied the sequence dependent binding of 2-amino-1,8-naphthyridine derivative 1 to a single guanine bulge. The free energy changes for the binding to a guanine bulge with different sequence contexts (5′X_Y3′/3′X′GY′5′) were determined by a curve fitting of the thermal denaturation profile of DNA in the presence and absence of 1. The data showed that (i) the binding of 1 to a guanine bulge is stronger for those flanking the G–C base pair than A–T base pair, (ii) the guanine 3′ side to 1 in the complex is especially effective for the complex stabilization, and (iii) the increase of T m in the presence of 1 is not a good estimate for the sequence dependent binding. The most efficient 1-binding was observed for the sequence of G_G/CGC. Molecular modeling simulations suggested that stacking interaction between the 3′ side guanine and 1 is the molecular basis for the strong binding to G_G/CGC. The sequence dependency for the binding of naphthyridine derivative was investigated.