title: 2,6-diaminopurine nucleoside derivative of 9-ethyloxy-2-oxo-1,3-diazaphenoxazine (2-amino-Adap) for recognition of 8-oxo-dG in DNA.
abstract: 8-oxo-2'-deoxyguanosine (8-oxo-dG) is a nucleoside resulting from oxidative damage and is known to be mutagenic. 8-Oxo-dG has been related to aging and diseases, including neurological disorders and cancer. Recently, we reported that a fluorescent nucleoside derivative, adenosine-1,3-diazaphenoxazine (Adap), forms a stable base pair with 8-oxo-dG in DNA with accompanying efficient quenching. In this study, a new Adap derivative having an additional 2-amino group on the adenosine moiety (2-amino-Adap) was designed with the anticipation of additional hydrogen bonding with the 8-oxo group of 8-oxo-dG. The properties of the ODN containing 2-amino-Adap were evaluated by measuring thermal stability and fluorescence quenching. In contrast to the previously designed Adap, the base-pairing and fluorescence quenching properties of 2-amino-Adap varied depending on the ODN sequence, and there was no clear indication of an additional hydrogen bond with 8-oxo-dG. Instead, the base pairing of 2-amino-Adap with dG was significantly destabilized compared with that of Adap with dG, resulting in improved selectivity for 8-oxo-dG in the human telomere DNA sequence. Thus, the telomere-targeting ODN probe containing 2-amino-Adap displayed selective, sensitive and quantitative detection of 8-oxo-dG in the human telomere DNA sequence in a light-up detection system using SYBR Green.
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: taniguch@phar.kyushu-u.ac.jp.
authors: Yosuke
authors: Y
authors: Taniguchi
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Keitaro
authors: K
authors: Fukabori
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Yoshiya
authors: Y
authors: Kikukawa
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Yohei
authors: Y
authors: Koga
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: sasaki@phar.kyushu-u.ac.jp.
authors: Shigeki
authors: S
authors: Sasaki
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D010078:Oxazines / Q000737:chemistry*
chemical_list: D009705:Nucleosides; D010078:Oxazines; D015075:2-Aminopurine; C007300:2,6-diaminopurine
keywords: 2-Oxo-1,3-diazaphenoxazine; 8-Oxo-2′-deoxyguanosine; Fluorescent nucleoside; Light-up detection; Oxidative damage; Telomere