Dye-containing macrocycles for recognition and detection of nucleotides

该项目旨在研究水溶液中核苷酸识别和传感的原理。该项目的几个部分涉及核碱基和序列选择性识别的新概念，而在其他部分，我们开发了具有前所未有的荧光响应的可视化结合方法。这两个方向的结果将有助于探索新的受体作为荧光标记和抗病毒感染和癌症的生物活性化合物。我们最近的实验揭示了环烷结构中间隔物对核苷酸选择性识别的重要性。现在，我们建议研究具有a)手性间隔，b)酰胺结合位点c)与核碱基偶联的新一代环烷。提出了一种二聚化方法，以达到我们的胞嘧啶选择性受体的高亲和力。利用富含胞嘧啶寡核苷酸和DNA i-motif的光谱方法设计、合成和分析主客体结构。高亲和力结合将使我们能够研究我们的系统作为位点特异性结合物和酶分析中的荧光指标。提出了一个新的吡啶-萘酰亚胺受体家族，在核苷酸和寡核苷酸的存在下具有创纪录的荧光增强。荧光信号的产生是基于通过超分子络合阻止两个有效的分子内PET过程。计划对受体的特性和核苷酸结合进行详细的研究，以深入了解其结合和传感机制。

The project aims to investigate principles of nucleotide recognition and sensing in an aqueous solution. Several parts of the project deal with new concepts for nucleobase- and sequences selective recognition, while in other parts, we develop approaches to visualize the binding with unprecedented fluorescence response. The results of both directions will enable in an exploration of new receptors as fluorescence markers and as biologically active compounds against viral infections and cancer. Our recent experiments have revealed the importance of spacers in the structure of cyclophanes for the selective recognition of nucleotides. Now, we propose to study a new generation of cyclophanes bearing a) chiral spacers, b) amide binding sites c) conjugation with nucleobases. A dimerization approach is proposed to reach high affinity of our cytosine-selective receptors. The design, synthesis, and analysis of host-guest structures using spectroscopic methods with cytosine-rich oligos and DNA i-motif will be carried out. High-affinity binding will enable us to investigate our systems as site-specific binders and as fluorescent indicators in enzymatic assays. A new family of pyridinium-naphthalimide receptors is proposed with a record fluorescence enhancement in the presence of nucleotides and oligos. The fluorescence signal generation is based on hindering two efficient intramolecular PET processes by supramolecular complexation. Detailed studies of the receptor's properties and nucleotide binding are planned to get insights into the binding and sensing mechanisms.