Development and application of glycan readers for the detection and analysis of bacterial glycoconjugates

用于细菌糖复合物检测和分析的聚糖读数器的开发和应用

基本信息

项目摘要

Project Summary The glycans that decorate cell-surface glycoconjugates, represent a rich molecular language that mediates a myriad of important biological functions. In bacteria, these glycoconjugates are critical determinants in interactions amongst bacterial communities and between both pathogenic and symbiotic bacteria and human host cells. A major challenge in understanding the roles of complex glycans in bacteria is that the pool of monosaccharide building blocks and diversity of glycosidic linkages reflected in the glycoconjugates is greatly expanded relative to eukaryotic organisms. Therefore, the currently-available glycan-binding proteins, which include lectins and monoclonal antibodies, are simply inadequate for detecting a majority bacterial glycan epitopes. In light of the importance of bacterial glycans in human infectious disease, the development of experimental reagents, as “glycan readers”, to selectively characterize and monitor pathogen-specific glycan determinants is of utmost current importance. Selective glycan readers towards bacterial glycan epitopes promise to be valuable reagents for identifying bacterial pathogens and understanding the biological significance of glycoconjugates in infectious disease.  In this exploratory research program, we aim to establish proof-of-principle for engineered protein-based glycan readers for the detection and analysis of pathogen-specific glycans and glycoconjugates. This proposal includes two aims. Aim 1 will involve preparation of chemically-defined C. jejuni glycan epitopes, including pseudaminic acid and N-acetyl bacillosamine, which are prokaryote-specific carbohydrates. These glycan epitopes will be armed, via established linker chemistry, with biotin for directed evolution of novel glycan binding proteins, based on the Sso7d scaffold, using yeast surface display. Aim 2 will develop applications of the evolved modular glycan binders using protein engineering approaches, with a focus on utility for the study of disease-related bacterial glycans. In particular, sortase-mediated ligation will be applied for modifying the C- and N-termini of glycan binders to include fluorophores and biotin. These “glycan readers” will be valuable for applications including glycan array visualization, live and fixed imaging, fluorescence-activated cell sorting (FACS) and affinity chromatography. In addition, azide-modified glycan readers will be amenable to click chemistry-based conjugation reactions with alkynes enabling, for example, multivalent display to exploit avidity effects.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)

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Barbara Imperiali其他文献

Barbara Imperiali的其他文献

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{{ truncateString('Barbara Imperiali', 18)}}的其他基金

Acquisition of Octet Biolayer Interferometry system for MIT biophysics facility
为麻省理工学院生物物理设施采购 Octet Biolayer 干涉测量系统
  • 批准号:
    8640541
  • 财政年份:
    2014
  • 资助金额:
    $ 23.21万
  • 项目类别:
PGT Inhibitors Mapped From a Tunicamycin Blueprint
根据衣霉素蓝图绘制的 PGT 抑制剂
  • 批准号:
    8508008
  • 财政年份:
    2013
  • 资助金额:
    $ 23.21万
  • 项目类别:
PGT Inhibitors Mapped From a Tunicamycin Blueprint
根据衣霉素蓝图绘制的 PGT 抑制剂
  • 批准号:
    8607890
  • 财政年份:
    2013
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of Glycoprotein Biosynthesis in Gram-Negative Pathogens
革兰氏阴性病原体糖蛋白生物合成的抑制
  • 批准号:
    8420337
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of Prokaryote-Specific Saccharide Biosynthesis in Microbial Pathogens
微生物病原体中原核生物特异性糖生物合成的抑制
  • 批准号:
    9004701
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of prokaryote-specific saccharide biosynthesis in microbial pathogens
微生物病原体中原核生物特异性糖生物合成的抑制
  • 批准号:
    8235459
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of Glycoprotein Biosynthesis in Gram-Negative Pathogens
革兰氏阴性病原体糖蛋白生物合成的抑制
  • 批准号:
    8262295
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of Prokaryote-Specific Saccharide Biosynthesis in Microbial Pathogens
微生物病原体中原核生物特异性糖生物合成的抑制
  • 批准号:
    8757021
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of Prokaryote-Specific Saccharide Biosynthesis in Microbial Pathogens
微生物病原体中原核生物特异性糖生物合成的抑制
  • 批准号:
    9265228
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:
Inhibition of prokaryote-specific saccharide biosynthesis in microbial pathogens
微生物病原体中原核生物特异性糖生物合成的抑制
  • 批准号:
    8446469
  • 财政年份:
    2012
  • 资助金额:
    $ 23.21万
  • 项目类别:

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