Protein Labeling and Crosslinking by Covalent Aptamers

共价适体的蛋白质标记和交联

基本信息

项目摘要

PROJECT SUMMARY The overall goal of this proposal is to develop a fundamentally new class of oligonucleotide agents – covalent aptamers – that will have a major impact on nucleic acid-based reagents and therapeutics. Covalent aptamers will be an enabling methodology behind new aptamer applications and will provide new solutions to persistent limitations of this compound class. Aptamers are engineered oligonucleotides that bind protein targets and have found applications in a multitude of areas, including therapeutics, diagnostics, drug delivery, and imaging. They bind their targets with affinity and specificity that rivals those of antibodies, while displaying lower production cost, higher production consistency, and the ability to easily introduce chemical modifications. Capitalizing on the ability to amplify and sequence nucleic acids, aptamers are being generated through SELEX, a powerful in vitro selection process. Our central hypothesis is that the formation of a covalent bond between an aptamer – or a functional motif delivered by the aptamer – and its target protein will provide unprecedented residence time, increase nuclease stability (or obviate the need for it), and facilitate aptamer selection. Furthermore, covalent bond formation enables new applications based on the aptamer platform. The following aims will test this hy- pothesis. Aim 1: The chemistry of covalent aptamers. To gain a comprehensive understanding of the design principles behind covalent aptamers and to enable broad applicability, we will explore their chemistry based on our promising preliminary results. We will explore applications in antibody drug conjugate assembly, as well as catalytic covalent bond formation. Aim 2: Cell-based applications of covalent aptamers. We will develop several applications that are enabled by covalent aptamers and that showcase their utility as chemical biology probes. We are focusing on cell-surface proteins due to the rich collection of aptamers that have been reported. Aim 3: Selection of covalent aptamers. For the de novo generation of covalent aptamers capable of selectively cross- linking to any chosen protein target without prior sequence and/or structural information, we will develop a gen- eralized in vitro selection process that adds distinct advantages to traditional SELEX.
项目总结

项目成果

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Alexander Deiters其他文献

Alexander Deiters的其他文献

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{{ truncateString('Alexander Deiters', 18)}}的其他基金

Protein Labeling and Crosslinking by Covalent Aptamers
共价适体的蛋白质标记和交联
  • 批准号:
    10391640
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
Conditional Control of Drug Function Through α-Boryl Ether Oxidation
通过α-硼基醚氧化条件控制药物功能
  • 批准号:
    9895812
  • 财政年份:
    2019
  • 资助金额:
    $ 35.65万
  • 项目类别:
Conditional Control of Drug Function Through α-Boryl Ether Oxidation
通过α-硼基醚氧化条件控制药物功能
  • 批准号:
    9750473
  • 财政年份:
    2019
  • 资助金额:
    $ 35.65万
  • 项目类别:
Conditional Control of Drug Function Through α-Boryl Ether Oxidation
通过α-硼基醚氧化条件控制药物功能
  • 批准号:
    10380804
  • 财政年份:
    2019
  • 资助金额:
    $ 35.65万
  • 项目类别:
Optical Control of Translation and Gene Editing in Zebrafish Embryos
斑马鱼胚胎翻译和基因编辑的光学控制
  • 批准号:
    9357624
  • 财政年份:
    2016
  • 资助金额:
    $ 35.65万
  • 项目类别:
High-Throughput Assay for the Discovery of Small Molecule Inhibitors of microRNA
用于发现 microRNA 小分子抑制剂的高通量检测
  • 批准号:
    8299685
  • 财政年份:
    2010
  • 资助金额:
    $ 35.65万
  • 项目类别:
High-Throughput Assay for the Discovery of Small Molecule Inhibitors of microRNA
用于发现 microRNA 小分子抑制剂的高通量检测
  • 批准号:
    8050335
  • 财政年份:
    2010
  • 资助金额:
    $ 35.65万
  • 项目类别:
Switchable Systems for Spatio-Temporal Control of Gene Expression in Zebrafish
用于斑马鱼基因表达时空控制的可切换系统
  • 批准号:
    8004512
  • 财政年份:
    2010
  • 资助金额:
    $ 35.65万
  • 项目类别:
Switchable Systems for Spatio-Temporal Control of Gene Expression in Zebrafish
用于斑马鱼基因表达时空控制的可切换系统
  • 批准号:
    7465438
  • 财政年份:
    2007
  • 资助金额:
    $ 35.65万
  • 项目类别:
Switchable Systems for Spatio-Temporal Control of Gene Expression in Zebrafish
用于斑马鱼基因表达时空控制的可切换系统
  • 批准号:
    7617674
  • 财政年份:
    2007
  • 资助金额:
    $ 35.65万
  • 项目类别:

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