Defining, studying, and targeting sulfated tyrosine residues of cell surface receptors for disease treatment
定义、研究和靶向细胞表面受体的硫酸化酪氨酸残基用于疾病治疗
基本信息
- 批准号:10504069
- 负责人:
- 金额:$ 30.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAffinityAmino Acid SequenceAreaBindingBiochemicalBiologicalBiological ProcessBiologyBiomedical ResearchCXCR4 ReceptorsCardiovascular DiseasesCell AdhesionCell Surface ReceptorsCell physiologyCellular biologyChronicDataData SetDevelopmentDiseaseEngineeringEventFoundationsGenerationsGeneticGoalsHematological DiseaseHormonesHumanImmune responseInflammatoryKnowledgeLeukocyte TraffickingLigand BindingLigandsLiteratureLung diseasesMammalian CellMass Spectrum AnalysisMedicalMethodologyMethodsN-terminalNaturePathologicPathologyPhysiologicalPhysiological ProcessesPlayProcessProteinsReceptor SignalingResearchRoleScaffolding ProteinSignal PathwaySignal TransductionSolidSulfateSystemTherapeutic InterventionTimeTyrosineWorkantibody mimeticsbasechemokinechemokine receptordrug developmentextracellularhuman diseaseinfancyinsightinstrumentationinterestmethod developmentnovelnovel therapeutic interventionnovel therapeuticspreferencepreventprogramsreceptorreceptor functionsuccesstargeted treatmenttherapeutic targettooltyrosine O-sulfate
项目摘要
Project Summary
Protein tyrosine O-sulfation (PTS) of cell surface receptors plays a crucial role in extracellular biomolecular
interactions that dictate various cellular processes, including cell adhesion, leukocyte trafficking, hormone
activities, and immune responses. Tyrosine-sulfated receptors also participate in the development of various
human diseases. Accordingly, PTS could emerge as an important drug target for the treatment of human
diseases. Despite substantial advances in our knowledge of PTS, our current understanding of its biological
significance is still in its infancy. It is this knowledge gap we seek to fill. In one direction, we will conduct
comprehensive and discovery-based sulfoproteomic studies, which will lay the foundation to unveil the entire
human receptor sulfointeractome and to identify disease-related sulfoprotein-protein interactions. In the
second direction, we seek to define the role of PTS in the function of chemokine receptors. Chemokine
signaling is central to chronic inflammatory conditions and participates in the development of many human
diseases. At their N-terminal region, chemokine receptors contain tyrosine residues that can be sulfated to
different extent (designated as “PTS level”). Our hypothesis is that chemokine receptors (and possibly other
cell surface receptors in general) can be sulfated to various PTS levels, which allows the receptors to bind
different ligands and leads to altered downstream biological/pathological events. In addition to basic
mechanistic studies, we also seek to explore and develop novel therapeutic agents targeting PTS of
chemokine receptors, such as C-X-C chemokine receptor type 4 (CXCR4). CXCR4 plays important roles in
both physiological and pathological conditions, and it represents a crucial target in drug development. Our
proposed work will be enabled by three technological breakthroughs, including the engineering of
sulfotyrosine-recognizing small protein scaffolds, the use of state-of-the-art mass spectrometry methods, and
the development of genetic method to encode sulfotyrosine in mammalian cells. Overall, the successful
completion of the proposed work is expected to yield comprehensive data on receptor sulfoproteome, to gain
insights into PTS-associated cellular biology, and to produce novel therapeutic interventions of human
diseases.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Engineering of SH2 Domains for the Recognition of Protein Tyrosine O-Sulfation Sites.
用于识别蛋白质酪氨酸 O-硫酸化位点的 SH2 结构域工程。
- DOI:10.1007/978-1-0716-3393-9_16
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Waldrop,SeanPaul;Niu,Wei;Guo,Jiantao
- 通讯作者:Guo,Jiantao
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Jiantao Guo其他文献
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{{ truncateString('Jiantao Guo', 18)}}的其他基金
Developing synthetic chemical biology strategies for biochemical investigations and biomedical applications
开发用于生化研究和生物医学应用的合成化学生物学策略
- 批准号:
10623497 - 财政年份:2023
- 资助金额:
$ 30.1万 - 项目类别:
Development of proximity-induced fluorogenic reactions for imaging biomolecular interaction through noncanonical amino acid mutagenesis in response to quadruplet codon and recoding signal
开发邻近诱导的荧光反应,通过响应四联体密码子和重新编码信号的非规范氨基酸诱变来成像生物分子相互作用
- 批准号:
10033286 - 财政年份:2020
- 资助金额:
$ 30.1万 - 项目类别:
Development of proximity-induced fluorogenic reactions for imaging biomolecular interaction through noncanonical amino acid mutagenesis in response to quadruplet codon and recoding signal
开发邻近诱导的荧光反应,通过响应四联体密码子和重新编码信号的非规范氨基酸诱变来成像生物分子相互作用
- 批准号:
10259702 - 财政年份:2020
- 资助金额:
$ 30.1万 - 项目类别:
Nebraska Center for Integrated Biomolecular Communication (CIBC)
内布拉斯加州综合生物分子通讯中心 (CIBC)
- 批准号:
10488641 - 财政年份:2016
- 资助金额:
$ 30.1万 - 项目类别:
Nebraska Center for Integrated Biomolecular Communication (CIBC)
内布拉斯加州综合生物分子通讯中心 (CIBC)
- 批准号:
10704185 - 财政年份:2016
- 资助金额:
$ 30.1万 - 项目类别:
Nebraska Center for Integrated Biomolecular Communication (CIBC)
内布拉斯加州综合生物分子通讯中心 (CIBC)
- 批准号:
10271829 - 财政年份:2016
- 资助金额:
$ 30.1万 - 项目类别:
Improve the safety of an efficacious live-attenuated HIV-1 vaccine through unnatu
通过 unnatu 提高有效的 HIV-1 减毒活疫苗的安全性
- 批准号:
8706615 - 财政年份:2014
- 资助金额:
$ 30.1万 - 项目类别:
Improve the safety of an efficacious live-attenuated HIV-1 vaccine through unnatu
通过 unnatu 提高有效的 HIV-1 减毒活疫苗的安全性
- 批准号:
8837571 - 财政年份:2014
- 资助金额:
$ 30.1万 - 项目类别:
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