基于超分子组装体的多位点生物分子传感平台的构建及应用

Highly sensitive and selective recognition for biomolecules are of great significance for early diagnosis and treatment. It is a difficulty to realize the recognition of bioactive molecules with multi-binding sites, because the design of such probes requires not only the introduction of multiple binding sites, but also the spatial matching between probe binding sites and analytes. These probes also require cumbersome organic synthesis, and the recognition results are usually unpredictable. Supramolecular assemblies could provide multiple binding sites with regulatable spatial orientation simultaneously which are more suitable to bind with analytes. The higher local concentrations of binding sites in assemblies can enhance the affinity with analytes. Based on the above factors, assemblies could exhibit excellent sensitivity and selectivity to biomolecule recognition. This project intends to design perylene or cyanine dyes with functional groups, such as, boronic acid group, aldehyde group, mercapto group, positive/negative charges or hydrogen bond donor/acceptor. The association and dissociation processes of their assemblies could recognize biomolecules containing multi-binding sites (such as NADH, ATP, dopamine, glucosamine, glutathione, etc.) with high sensitivity and selectivity. We also try to apply them to the biological samples for actual analysis. Supramolecular assemblies act as a kind of functional materials that are currently attracting much attention, and this project is expected to provide new ideas for their applications and to provide a new approach for the identification of biomolecules containing multiple binding sites.

生物活性小分子的高灵敏度和强选择性识别在疾病预防、早期诊疗方面具有重要意义。实现多结合位点生物分子的检测是分子识别领域的一个难点，设计该类探针不仅需要引入多个结合位点，还应考虑到探针结合位点与分析物之间的空间匹配性，通常合成难度较大，且具有不可预测性。超分子组装体可同时提供多个结合位点，组装单元之间空间排布易于调控，结合基团局部浓度较高，利于和多结合位点分析物结合并表现出优越的传感灵敏度和选择性。本项目拟设计含有硼酸基、醛基、巯基、正/负电荷以及氢键给/受体等功能位点的苝酰亚胺和花菁等染料分子，籍其组装体的形成-解离过程高灵敏高选择性地检测含多个结合位点的生物分子（如NADH、ATP、多巴胺、葡萄糖胺、谷胱甘肽等），并尝试将其应用于生物实际样品的分析检测中。超分子组装体作为一类目前广受关注的功能性材料，本项目期望为其应用给出新的思路，也为含有多个结合位点的生物小分子的识别提供新的研究途径。

对重大疾病的准确诊断和有效防控，能够有力保障人们的健康，一直以来都是疾病防控的核心任务。疾病相关活性物质的选择性和高灵敏检测可为其早期诊断提供技术支撑。本项目针对疾病的标志性物质，以生命体内的活性分子(包括离子、活性氧/硫/氮、生物酶等)为分析目标，向苝酰亚胺和花菁等有机染料分子中合理地引入功能为点，高灵敏高选择性地检测具有重要生理意义的生物分子，并优化筛选有机染料分子引入的官能团结构和分析测试条件，希望提高对分析物检测的灵敏度和选择性。本项目实现了一系列生命活性物质的精准检测与活性动态监测，为疾病的早期诊断提供重要的参考价值，并取得了系列具有创新性的研究成果。具体的研究成果有：1）设计合成了新型荧光分子探针，使其具有低背景噪声的优点，提高了荧光探针的选择性和灵敏度，降低了细胞内背景荧光的干扰，减少了仪器噪音、探针浓度等客观因素的影响，并成功应用于细胞内生物分子的检测，为细胞内生物分子的荧光检测提供了新的方法和思路。2）设计制备了多种良好生物相容性的逻辑性双靶标荧光分子探针，发展了同时检测多种细胞内活性物质的荧光检测和成像新方法，成功避免了由于其单靶标在特定情况下造成的假阳性反应，实现了不同疾病的快速筛查和细胞及活体成像研究。