Dramatic fluorescence quenching of small heterocyclic ligands trapped in the abasic site (AP) of DNA has been implemented as an unprecedented strategy recognizing single-base mutations in sequence analysis of cancer genes. However, the key mechanisms governing selective nucleobase recognition remain to be disentangled. Herein, we perform fluorescence quenching dynamics studies for 2-amino-7-methyl-1,8-naphthyridine (AMND) in well-designed AP-containing DNA single/double strands. The primary mechanism is discovered, showing that AMND only targets cytosine to form a pseudo-base pair, and therefore, fluorescence quenching of AMND arises through the DNA-mediated electron transfer (ET) between excited state AMND* and flanking nucleobases, most favorably with flanking guanines. Subtle dynamic conformational variations induced by different flanking nucleobases are revealed and found to modulate efficiencies of electron transfer and fluorescence quenching. These findings provide critical mechanistic insights for guiding the design of photoinduced electron transfer (PET)-based fluorescent ligands as sensitive single-base recognition reporters.

中文翻译：

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用于核碱基识别的含无碱基位点 DNA 双链体中 2-氨基-7-甲基-1,8-萘啶的荧光猝灭动力学

捕获在 DNA 脱碱基位点 (AP) 中的小杂环配体的显着荧光猝灭已被实施为一种前所未有的策略，用于识别癌症基因序列分析中的单碱基突变。然而，控制选择性核碱基识别的关键机制仍有待解开。在此，我们对精心设计的含 AP DNA 单链/双链中的 2-氨基-7-甲基-1,8-萘啶 (AMND) 进行荧光猝灭动力学研究。主要机制被发现，表明 AMND 仅靶向胞嘧啶形成假碱基对，因此 AMND 的荧光猝灭是通过激发态 AMND* 和侧翼核碱基之间 DNA 介导的电子转移 (ET) 产生的，最有利的是侧翼鸟嘌呤。揭示了不同侧翼核碱基诱导的微妙动态构象变化，并发现它们可以调节电子转移和荧光猝灭的效率。这些发现为指导基于光诱导电子转移（PET）的荧光配体作为敏感单碱基识别报告基因的设计提供了关键的机制见解。