Development of new fluorescent probes for nucleic acids based on aminophthalimide as isosteric base substitution and photostable cyanine-styryl dyes

基于氨基邻苯二甲酰亚胺作为等排碱基取代和光稳定性花青苯乙烯基染料的新型核酸荧光探针的开发

基本信息

项目摘要

Fluorescent labeling plays not only a major role in chemical bioanalytics and molecular diagnostics, but also in the actually strongly expanding research field of molecular imaging of living cells. The central goal of this project remains to be the development of new fluorescent probes for nucleic acids, which are suitable for chemical biology based on their optimized structure and optical properties, and can replace weaker, but commercially available fluorescent probes. The focus of this project in the first funding period was the development of new fluorescent probes for DNA based on aminophthalimide that is isosteric to purines, and photostable cyanine-styryl dyes as postsynthetic modifications for DNA, as described in the project report and documented by publications. During the second funding period we propose to shift the focus onto RNA and develop these fluorescent probes for RNA. The particular challenges are still divided into two subprojects: (A) Isosteric probes with fluorophores that have approximately the small size of DNA/RNA bases but nonetheless show large Stokes’ shifts and applicable quantum yields are important because they do only slightly alter the structure of nucleic acids and their biological interactions (subproject A). In the first funding period, we established aminophthalimide as base surrogate for DNA. It should now be developed and established as RNA probe. (B) For the bioorthogonally and “clickable” fluorescent probes not only photostability is important for the application in long-lasting cellular imaging by single molecule spectroscopy, but also fluorogenic properties are determing these applications. The latter will be a new criterium for the second funding period. Fluorogenic probes have the great advantage that only those fluorophores are lighting up by their enhanced emission which are conjugated to RNA (and DNA) (subproject B). Taken together, this project will deliver new and powerful fluorescent probes for RNA bioanalytics and imaging.
荧光标记不仅在化学生物分析和分子诊断中发挥着重要的作用,而且在活细胞的分子成像研究领域也是一个正在大力发展的研究领域。该项目的中心目标仍然是开发新的核酸荧光探针,这种探针基于其优化的结构和光学性质适合于化学生物学,并可以取代较弱的但商业上可用的荧光探针。该项目在第一个供资期间的重点是开发基于氨基邻苯二甲酰亚胺的新的DNA荧光探针,该荧光探针与嘌呤是同位异构体,以及作为DNA的合成后修饰的光稳定的菁苯基染料,如项目报告所述和出版物所述。在第二个资助期,我们建议将重点转移到RNA上,并开发这些用于RNA的荧光探针。具体的挑战仍然分为两个次级项目:(A)带有荧光团的同位素体探针,其尺寸大约与DNA/RNA碱基一样小,但仍然显示出大的斯托克斯位移和适当的量子产率,这一点很重要,因为它们只略微改变了核酸的结构及其生物相互作用(次级项目A)。在第一个资助期,我们建立了氨基邻苯二甲酰亚胺作为DNA的碱基替代品。它现在应该被开发和建立为RNA探针。(B)对于生物正交性和“可点击”的荧光探针,不仅光稳定性对于单分子光谱学在长时间细胞成像中的应用是重要的,而且荧光特性也决定了这些应用。后者将成为第二个资助期的新标准。荧光探针有一个很大的优势,那就是只有那些与RNA(和DNA)结合的荧光团才会通过增强发射而发光(子项目B)。总而言之,该项目将为RNA生物分析和成像提供新的强大的荧光探针。

项目成果

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Professor Dr. Hans-Achim Wagenknecht其他文献

Professor Dr. Hans-Achim Wagenknecht的其他文献

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{{ truncateString('Professor Dr. Hans-Achim Wagenknecht', 18)}}的其他基金

Chemical photocatalysis with oligonucleotides and short peptides
寡核苷酸和短肽的化学光催化
  • 批准号:
    255037740
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Postsynthetic modifications of DNA and RNA by bioorthogonal reactions
通过生物正交反应对 DNA 和 RNA 进行合成后修饰
  • 批准号:
    233936261
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Metal ion-mediated electron transfer in supramolecular DNA architectures
超分子 DNA 结构中金属离子介导的电子转移
  • 批准号:
    101434803
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Nachweis von Punktmutationen mit Hilfe photoelektronischer Wechselwirkungen zwischen zwei fluoreszenten Basensurrogaten
利用两个荧光碱基替代物之间的光电相互作用检测点突变
  • 批准号:
    5434716
  • 财政年份:
    2004
  • 资助金额:
    --
  • 项目类别:
    Research Grants
DNA-Systeme für die zeitaufgelöste Beobachtung und zur Modulation des reduktiven Elektronentransfers durch die DNA
用于时间分辨观测和调节 DNA 还原电子转移的 DNA 系统
  • 批准号:
    5326894
  • 财政年份:
    2001
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Synthese photoreaktiver Sialylglykokonjugate zur Untersuchung der Kohlenhydrat-Kohlenhydrat-Wechselwirkungen von Tumorzellen
合成光反应性唾液酸糖缀合物以研究肿瘤细胞的碳水化合物-碳水化合物相互作用
  • 批准号:
    5317136
  • 财政年份:
    2001
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Oxidation of DNA-bound peptides and proteins by DNA-mediated electron transfer reactions
DNA 介导的电子转移反应氧化 DNA 结合的肽和蛋白质
  • 批准号:
    5252952
  • 财政年份:
    2000
  • 资助金额:
    --
  • 项目类别:
    Emmy Noether International Fellowships
Metabolic labeling of RNA by means of synthetic and bioorthogonally reactive nucleoside as fluorogenic probes in living cells
通过合成和生物正交反应核苷作为活细胞中的荧光探针对 RNA 进行代谢标记
  • 批准号:
    461961063
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Photoredox catalytic activation of sulfur hexafluoride for the synthesis of pentafluorosulfanylated organic compounds
光氧化还原催化活化六氟化硫合成五氟磺酰化有机化合物
  • 批准号:
    505932961
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants

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