Effect of an alkyl amino group on the binding of 1,8-naphthyridines to AP site-containing DNA duplexes.

A 1,8-naphthyridine derivative having a positively charged side-chain, N-(3-aminopropyl)-5,6,7-trimethyl-1,8-naphthyridine-2-amine (APATMND), is synthesized, and its binding to AP site-containing DNA duplexes (5'- GCA GCT CCC GXG GTC TCC TCG-3'/ 5'-CGA GGA GAC CNC GGG AGC TGC-3', X = AP site; dSpacer, N = C, T) is examined in solutions buffered to pH 7.0 (I = 0.11 M, at 20 degrees C). Fluorescence titration experiments reveal that, as compared to a parent ligand, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), capable of selectively binding C over T opposite an AP site in the duplex (K(d)/nM: C: 56, T: 100), APATMND shows a stronger binding affinity for T, while an affinity for C is reduced (K(d)/nM: C: 135, T: 37). An examination of salt dependence of binding constants reveals that a polyelectrolyte contribution (Delta G(pe)) is indeed increased for C- and T-bindings of APATMND, but a loss of non-polyelectrolyte contribution (Delta G(t)) is significant when binding to C. These binding properties of APATMND are discussed with a view towards further development of DNA-binding ligands suitable for gene detection.