title: Strong binding of naphthyridine derivatives to cytosine in an AP site-containing DNA duplex and their application to fluorescence detection of single nucleotide polymorphisms.
abstract: Here we report on a significant enhancement of the binding affinity of naphthyridine-based fluorescence ligands that can selectively bind to cytosine opposite an AP site in a DNA duplex (5'-TCC AGX GCA AC-3'/3'-AGG TCC CGT TG -5', X = AP site, C = target). We have previously reported that 2-amino-7-methyl-1,8-naphthyridine (AMND) binds to cytosine with a dissociation constant of 370 nM (pH 7.0, I = 0.11 M, at 20 degrees C). In this work, AMND is modified simply by introducing two methyl groups to the naphthyridine ring. The present ligand, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), shows a stronger binding affinity for cytosine, and a dissociation constant reaches 56 nM. ATMND is effectively applicable to the analysis of cytosine-related mutation of PCR products. These promising abilities of ATMND are presented based on the examination by melting temperature (T(m)) and fluorescence measurements.
authors.affiliation: Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Takehiro
authors.initials: T
authors.lastname: Seino
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Norio
authors.initials: N
authors.lastname: Teramae
mesh_terms: D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D009287:Naphthyridines / Q000737:chemistry*; D009691:Nucleic Acid Denaturation; D020641:Polymorphism, Single Nucleotide
chemical_list: C528376:2-amino-5,6,7-trimethyl-1,8-naphthyridine; C520210:2-amino-7-methyl-1,8-naphthyridine; D005456:Fluorescent Dyes; D009287:Naphthyridines; D003596:Cytosine; D004247:DNA