DNA脱碱基位点的检测与应用

Detection and Application of DNA Abasic Sites

脱碱基位点是一种常见的DNA损伤,源于N-糖苷键断裂而使碱基脱落。辐射、烷基化试剂和一些抗癌药物等可能会造成碱基脱落,因此脱碱基位点作为标志性损伤能够帮助疾病早期筛查、药物毒副作用评价、环境污染物毒性评价等。目前已有不同的检测方法用于脱碱基位点的定量、定性分析,包括32P后标记法、LC-MS、ELISA及化学探针检测法等。另一方面,由于脱碱基位点在双链DNA内形成疏水空腔,能够结合小分子,使得脱碱基位点作为结合位点被用于小分子检测、构建适配体传感器及SNP检测。本文简要概述目前为止对DNA脱碱基位点的化学探针检测法研究进展以及含有脱碱基位点DNA的应用研究进展,并展望其发展趋势。

Abasic sites （apurinic/apyrimidinic or AP sites）, a common lesion in DNA, are resulted from the cleavage of n-glycosylic bond, leaving deoxyribose residue in DNA. AP sites have emerged as the mutation/ cancer markers and attracted great attention. A variety of analytical methods have been developed for the determination and quantification of AP sites in DNA, including 32 p post-labeling, LC-MS, and ELISA. In this article, we provided an overview on the recent development of the DNA AP site detection using synthetic chemical probes. Covalent chemical probes were designed and synthesized which showed high specificity toward a particular AP site structure. Signal report groups were directly attached to the probe either, or indirectly by affinity reactions. Alternatively, non-covalent probes with signal groups rely on the weak （hydrogen-bonding, electrostatic, base stacking ）interactions with the AP site and the consequent signal modulation. In addition, the AP sites have been explored as a recognition element in the detection of small molecules and SNPs.