Wang Ying, Hu Yuehua, Wu Tao, Zhang Lihua, Liu Hua, Zhou Xiaoshun, Shao Yong
Institute of Physical Chemistry, Zhejiang Normal University, Jinhua 321004, Zhejiang, People's Republic of China.
Institute of Physical Chemistry, Zhejiang Normal University, Jinhua 321004, Zhejiang, People's Republic of China.
Spectrochim Acta A Mol Biomol Spectrosc. 2016 Jan 15;153:645-50. doi: 10.1016/j.saa.2015.09.038.
Removal of a damaged base in DNA produces an abasic site (AP site) nanocavity. If left un-repaired in vivo by the specific enzyme, this nanocavity will result in nucleotide mutation in the following DNA replication. Therefore, selective recognition of AP site nanocavity by small molecules is important for identification of such DNA damage and development of genetic drugs. In this work, we investigate the fluorescence behavior of isoquinoline alkaloids including palmatine (PAL), berberine (BER), epiberberine (EPI), jatrorrhizine (JAT), coptisine (COP), coralyne (COR), worenine (WOR), berberrubine (BEU), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT) upon binding with the AP nanocavity. PAL is screened out as the most efficient fluorophore-switched probe to recognize the AP nanocavity over the fully matched DNA. Its fluorescence enhancement occurs for all of the AP nanocavity sequence environments, which has not been achieved by the previously used probes. The bridged π conjugation effect should partially contribute to the AP nanocavity-specific fluorescence, as opposed to the solvent effect. Due to the strong binding with the AP nanocavity, PAL will find wide applications in the DNA damage recognition and sensor development.
去除DNA中受损的碱基会产生一个无碱基位点（AP位点）纳米腔。如果在体内未被特定酶修复，这个纳米腔会在随后的DNA复制中导致核苷酸突变。因此，小分子对AP位点纳米腔的选择性识别对于此类DNA损伤的鉴定和基因药物的开发至关重要。在这项工作中，我们研究了异喹啉生物碱包括巴马汀（PAL）、小檗碱（BER）、表小檗碱（EPI）、药根碱（JAT）、黄连碱（COP）、珊瑚菜碱（COR）、吴茱萸碱（WOR）、小檗红碱（BEU）、血根碱（SAN）、白屈菜红碱（CHE）和两面针碱（NIT）与AP纳米腔结合后的荧光行为。PAL被筛选为在识别AP纳米腔方面比完全匹配的DNA更有效的荧光团切换探针。在所有AP纳米腔序列环境中它都会发生荧光增强，这是以前使用的探针所未实现的。与溶剂效应相反，桥连的π共轭效应应该部分促成了AP纳米腔特异性荧光。由于与AP纳米腔的强结合，PAL将在DNA损伤识别和传感器开发中找到广泛应用。
