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

• Published in: Nucleic Acids Symposium Series 2008-09, Vol.52 (1), p.117-118
• Main Authors: Ichihashi, Toshiki, Sato, Yusuke, Seino, Takehiro, Nishizawa, Seiichi, Teramae, Norio
• Format: Article
• Language: English
• ISSN: 0261-3166; 1746-8272
• DOI: 10.1093/nass/nrn060

Abstract A 1,8-naphthyridine derivative having a positively charged side-chain, N-(3-aminopropyl)-5,6,7-trimethyl-1,8-naphthyridin-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°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 (Kd/nM: C: 56, T: 100), APATMND shows a stronger binding affinity for T, while an affinity for C is reduced (Kd/nM: C: 135, T: 37). An examination of salt dependence of binding constants reveals that a polyelectrolyte contribution (ΔGpe) is indeed increased for C- and T-bindings of APATMND, but a loss of non-polyelectrolyte contribution (ΔGt) 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.