3-O-sulfation of heparan sulfate as a regular of protein function

硫酸乙酰肝素的 3-O-硫酸化作为蛋白质功能的调节

基本信息

  • 批准号:
    10615737
  • 负责人:
  • 金额:
    $ 45.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-05-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Project summary/abstract Heparin is a highly sulfated carbohydrate produced by mast cells that is widely used as an anticoagulant to prevent deep vein thrombosis, pulmonary embolism and arterial thromboembolism. Heparan sulfate (HS) is structurally related to heparin and decorates the surface of all most all human cells. It interacts with a multitude of proteins including chemokines and cytokines; blood coagulation factors; growth factors and morphogens, proteins involved in complement activation, and cell adhesion and signaling proteins. HS has been implicated in human diseases such as vascular diseases, inflammation, infections and neurodegeneration. It has been postulated that HS encodes information by an ability to recruit proteins in a context-dependent manner. Although the “HS-sulfate code” hypothesis is conceptually appealing, little is known about the ligand specificities of HS binding proteins and the substrate specificities of HS-biosynthetic enzymes. As a result, it is not known whether isoforms of HS biosynthetic enzymes can create distinctive epitopes that in a cellular context can recruit specific HS- binding proteins. An understanding of the specificities of HS binding also offers opportunities to develop therapeutic modalities. In this program, chemical and chemo-enzymatic methodologies will be developed that will make it possible to prepare a focused library of biologically relevant HS epitopes with and without a 3-O-sulfate moiety. These compounds will be used to develop an HS-microarray to establish ligand requirement of HS-binding proteins. Compounds of interest will be further explored for their ability to interfere in the binding and cellular activation of endothelial cells. We will focus on HS-binding proteins involved in blood coagulation, inflammation and vascular disease. The established structure-activity relationships are expected to provide therapeutic lead compounds. The HS-microarray will also be used as a general platform to discover and characterize HS-binding proteins requiring a 3-O-sulfate. In addition, the synthetic compounds will be used to define substrate requirements of the various 3-O-sulfotransferases. Collectively, our studies will address the question of whether isoforms of 3-O-sulfotransferases can create distinctive epitopes that can recruit specific HS-binding proteins, to mediate various biological processes. 1
项目总结/文摘

项目成果

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会议论文数量(0)
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Geert-Jan Boons其他文献

Geert-Jan Boons的其他文献

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{{ truncateString('Geert-Jan Boons', 18)}}的其他基金

Automated chemo-enzymatic synthesis of N-glycans for host-pathogen interactions
用于宿主-病原体相互作用的 N-聚糖自动化学酶合成
  • 批准号:
    10626153
  • 财政年份:
    2022
  • 资助金额:
    $ 45.17万
  • 项目类别:
Automated chemo-enzymatic synthesis of N-glycans for host-pathogen interactions
用于宿主-病原体相互作用的 N-聚糖自动化学酶合成
  • 批准号:
    10521604
  • 财政年份:
    2022
  • 资助金额:
    $ 45.17万
  • 项目类别:
Synthetic multi-component influenza vaccines to elicit broad immunity
合成多成分流感疫苗可引发广泛免疫力
  • 批准号:
    10458316
  • 财政年份:
    2021
  • 资助金额:
    $ 45.17万
  • 项目类别:
3-O-sulfation of heparan sulfate as a regular of protein function
硫酸乙酰肝素的 3-O-硫酸化作为蛋白质功能的调节
  • 批准号:
    10400697
  • 财政年份:
    2020
  • 资助金额:
    $ 45.17万
  • 项目类别:
Streamlining the chemoenzymatic synthesis of asymmetrical glycans of biological importance
简化具有生物学重要性的不对称聚糖的化学酶合成
  • 批准号:
    9752086
  • 财政年份:
    2016
  • 资助金额:
    $ 45.17万
  • 项目类别:
Streamlining the chemoenzymatic synthesis of asymmetrical glycans of biological importance
简化具有生物学重要性的不对称聚糖的化学酶合成
  • 批准号:
    9533657
  • 财政年份:
    2016
  • 资助金额:
    $ 45.17万
  • 项目类别:
Streamlining the chemoenzymatic synthesis of asymmetrical glycans of biological importance
简化具有生物学重要性的不对称聚糖的化学酶合成
  • 批准号:
    9749989
  • 财政年份:
    2016
  • 资助金额:
    $ 45.17万
  • 项目类别:
Streamlining the chemoenzymatic synthesis of asymmetrical glycans of biological importance
简化具有生物学重要性的不对称聚糖的化学酶合成
  • 批准号:
    9166183
  • 财政年份:
    2016
  • 资助金额:
    $ 45.17万
  • 项目类别:
Mammalian Glycosyltransferases for use in Chemistry and Biology
用于化学和生物学的哺乳动物糖基转移酶
  • 批准号:
    8874755
  • 财政年份:
    2013
  • 资助金额:
    $ 45.17万
  • 项目类别:
Mammalian Glycosyltransferases for use in Chemistry and Biology
用于化学和生物学的哺乳动物糖基转移酶
  • 批准号:
    8740506
  • 财政年份:
    2013
  • 资助金额:
    $ 45.17万
  • 项目类别:

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  • 项目类别:
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