Strong binding of naphthyridine derivatives to a guanine base in DNA duplexes containing an AP site.
By using UV thermal denaturation and isothermal titration calorimetry (ITC), we examine the binding behaviors of a hydrogen bond-forming ligand, 2-acetylamino-7-methyl-1,8-naphthyridine (AcMND), with a guanine base opposite an abasic site (AP site) in a DNA duplex (5'-TCC AGX GCA AC-3'/3'-AGG TCG CGT TG-5', X = AP site, G = target). In the presence of AcMND, the melting temperature (Tm) of the AP site-containing DNA duplex increases by 8.6 degrees C while hardly any change in Tm is observed for a corresponding normal duplex that has no AP sites. The examination by ITC reveals that, in solutions buffered to pH 7.0 (at 10 degrees C, I = 0.11 M), AcMND is able to recognize guanine base with a 1:1 binding constant of 3.4x10(5) M(-1). The ligand-nucleotide interaction is clearly enthalpy driven, with deltaH(o) of -12.5 kcal/mol. We discuss these binding functions of AcMND at the AP site with a view towards development of ligand-based assay for SNPs (single-nucleotide polymorphisms) typing.
Gao
Qiang
Q
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Satake
Hiroyuki
H
Dai
Qing
Q
Ono
Katsuya
K
Nishizawa
Seiichi
S
Teramae
Norio
N
D002151:Calorimetry; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009287:Naphthyridines / Q000737:chemistry*; D009691:Nucleic Acid Denaturation; D020641:Polymorphism, Single Nucleotide
C520212:2-acetylamino-7-methyl-1,8-naphthyridine; D008024:Ligands; D009287:Naphthyridines; D006147:Guanine; D004247:DNA