Repurposing the Ribosome for Exotic Polymers

将核糖体重新用于外来聚合物

基本信息

  • 批准号:
    9311712
  • 负责人:
  • 金额:
    $ 24.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-01 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary: The machine used for template-guided protein synthesis–the ribosome and its associated translation factors–has been exploited for over 20 years to site-specifically incorporate > 150 unnatural α-amino acids and > 10 α-hydroxy acids into proteins, in vitro, in cells, and in animals. More exotic monomers, including N-alkyl α-amino acids, D-amino acids, and some β-amino acids have been incorporated using cell-free in vitro systems. These efforts have deepened our understanding of protein and RNA function and provided real-world commodities such as antibody-drug conjugates, modified therapeutics, and biomaterials to benefit society. Yet, even after two-plus decades of research, until very recently–the preliminary results for this application–there were no reports of a ribosome able to introduce a β-amino acid into a protein in vivo, nor any sophisticated bioinformatics tools for ribosome redesign. The goal of this application is to develop and apply genetic engineering, bioinformatics, and chemical biology tools to repurpose the bacterial translational apparatus for the templated, in vivo biosynthesis of proteins and polypeptides containing backbone-modified monomers. The primary focus is on β- amino acids, as preliminary results indicate that this goal is attainable with a 4-5 year RO1 award, but the strategies, insights, and tools developed will provide a robust infrastructure for the sequence-templated biosynthesis of diverse classes of evolvable matter–truly exotic biopolymers–whose functions are limited only by our collective imagination. By creating new machines that efficiently incorporate β-amino acids into proteins in vivo, we will not only provide tools to address enduring questions about natural translation, but also provide real benefit to diverse segments of bio-medical research engine.
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项目成果

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Alanna Schepartz其他文献

Alanna Schepartz的其他文献

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{{ truncateString('Alanna Schepartz', 18)}}的其他基金

Fluorescence tools that illuminate biology and inspire translation
阐明生物学并激发翻译的荧光工具
  • 批准号:
    10372854
  • 财政年份:
    2020
  • 资助金额:
    $ 24.08万
  • 项目类别:
Fluorescence tools that illuminate biology and inspire translation
阐明生物学并激发翻译的荧光工具
  • 批准号:
    10365915
  • 财政年份:
    2020
  • 资助金额:
    $ 24.08万
  • 项目类别:
Fluorescence tools that illuminate biology and inspire translation
阐明生物学并激发翻译的荧光工具
  • 批准号:
    10091496
  • 财政年份:
    2020
  • 资助金额:
    $ 24.08万
  • 项目类别:
Fluorescence tools that illuminate biology and inspire translation
阐明生物学并激发翻译的荧光工具
  • 批准号:
    10809483
  • 财政年份:
    2020
  • 资助金额:
    $ 24.08万
  • 项目类别:
Fluorescence tools that illuminate biology and inspire translation
阐明生物学并激发翻译的荧光工具
  • 批准号:
    10578832
  • 财政年份:
    2020
  • 资助金额:
    $ 24.08万
  • 项目类别:
Expanding the HIDE nanoscopy toolbox: More organelles, colors, and modalities
扩展 HIDE 纳米镜工具箱:更多细胞器、颜色和模式
  • 批准号:
    10019809
  • 财政年份:
    2019
  • 资助金额:
    $ 24.08万
  • 项目类别:
Repurposing the Ribosome for Exotic Polymers
将核糖体重新用于外来聚合物
  • 批准号:
    9999711
  • 财政年份:
    2017
  • 资助金额:
    $ 24.08万
  • 项目类别:
Directing the Mediator Complex: Bivalent approaches to Reconstituting or Inhibiti
指导介体复合体:重建或抑制的二价方法
  • 批准号:
    8895755
  • 财政年份:
    2012
  • 资助金额:
    $ 24.08万
  • 项目类别:
Foldamers: Novel Ligands for Diverse Protein Surfaces
Foldamers:用于多种蛋白质表面的新型配体
  • 批准号:
    7928434
  • 财政年份:
    2009
  • 资助金额:
    $ 24.08万
  • 项目类别:
Small Molecule Tools to Image and Understand Sophisticated Protein Function
用于成像和理解复杂蛋白质功能的小分子工具
  • 批准号:
    9276914
  • 财政年份:
    2008
  • 资助金额:
    $ 24.08万
  • 项目类别:

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