A chemical approach to elucidating the structure-function relationships of chondr
阐明软骨结构与功能关系的化学方法
基本信息
- 批准号:7918318
- 负责人:
- 金额:$ 39.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAffinity ChromatographyAgingAnabolismAntibodiesAxonBinding ProteinsBiochemistryBiologicalBiological ProcessBiologyBrainCarbohydratesCell CommunicationCellsCellular biologyChargeChemicalsChemistryChondroitin Sulfate AChondroitin Sulfate CChondroitin SulfatesCodeCrush InjuryDNADendritesDevelopmentDisaccharidesDiseaseEpitopesGenerationsGenesGeneticGlobal ChangeGrantGrowthImaging DeviceIn VitroInjuryInorganic SulfatesInvestigationLaboratoriesLearningMalignant NeoplasmsMammalsMass Spectrum AnalysisMemoryMolecularMolecular StructureMonoclonal AntibodiesMyelinNatural regenerationNerve CrushNervous system structureNeuritesNeurobiologyNeurodegenerative DisordersNeuronal InjuryNeuronsOligosaccharidesOptic NerveOrganic ChemistryPathway interactionsPatternPharmacologic SubstancePhysiologicalPhysiological ProcessesPlayPolysaccharidesProcessProteinsRNARegulationResearchRetinalRetinal Ganglion CellsRoleSourceSpinal cord injuryStructureStructure-Activity RelationshipSynapsesSynthesis ChemistryTestingTherapeutic InterventionUnspecified or Sulfate Ion SulfatesVariantViralWorkaxon growthaxon guidanceaxon regenerationcentral nervous system injurychondroitin sulfate glycosaminoglycandesigngrowth promoting activityin vivoinhibitor/antagonistinsightmarine organismmimeticsneural circuitneuron developmentneuronal growthneurotrophic factornovelnovel therapeutic interventionpolymerizationpreventpublic health relevancereceptorrepairedsmall moleculesulfationsulfotransferasetool
项目摘要
DESCRIPTION (provided by applicant): This project will focus on chondroitin sulfate (CS) glycosaminoglycans, a class of polysaccharides that play important roles in development, viral invasion, cancer, and spinal cord injury. CS polysaccharides display diverse sulfation patterns that are spatiotemporally regulated in vivo. However, efforts to identify functions for specific sulfation motifs have been hampered by the structural complexity of CS and a lack of tools. For instance, well-defined CS molecules cannot be purified from natural sources, and as a consequence, the field has been limited to working with heterogeneously sulfated mixtures of compounds. Genetic deletion of one of the sulfotransferase genes responsible for CS biosynthesis can propagate global changes throughout the carbohydrate chain, making it difficult to pinpoint the role of specific sulfation motifs. In this grant, we will combine the tools of organic chemistry and biology to overcome these challenges. We will exploit synthetic chemistry to assemble defined CS structures (both natural and non-natural) to obtain fundamentally new information about the structure- function relationships of CS. When combined with the power of biochemistry, genetics, cell biology, and neurobiology, these molecules will provide new insights into the physiological roles of carbohydrates in the nervous system and uncover novel mechanisms of neuronal growth and repair. As our project takes a distinctly chemical approach, this work may reveal novel proteins and pathways for therapeutic intervention and aid in the development of new pharmaceuticals to stimulate regeneration after injury, aging or disease.
PUBLIC HEALTH RELEVANCE: This research seeks to understand how the structure of chondroitin sulfate glycosaminoglycans regulates fundamental biological processes, such as protein recognition and regulation, cell-cell communication, development, and regeneration after injury. Through the discovery of novel small molecules, proteins and pathways involved in these processes, this work may aid ultimately in the development of new therapeutic approaches to a broad range of disease states, such as cancer, infectious and neurodegenerative diseases.
描述(由申请人提供):该项目将重点关注硫酸软骨素(CS)糖胺聚糖,这是一类在发育、病毒入侵、癌症和脊髓损伤中发挥重要作用的多糖。 CS多糖表现出多种在体内时空调节的硫酸化模式。然而,由于 CS 的结构复杂性和工具的缺乏,鉴定特定硫酸化基序功能的努力受到了阻碍。例如,明确定义的 CS 分子无法从天然来源中纯化,因此,该领域仅限于使用非均相硫酸化化合物混合物。负责 CS 生物合成的磺基转移酶基因之一的基因缺失可以在整个碳水化合物链中传播全局变化,从而很难确定特定硫酸化基序的作用。在这笔资助中,我们将结合有机化学和生物学的工具来克服这些挑战。我们将利用合成化学来组装定义的CS结构(天然和非天然),以获得有关CS结构功能关系的全新信息。当与生物化学、遗传学、细胞生物学和神经生物学的力量相结合时,这些分子将为碳水化合物在神经系统中的生理作用提供新的见解,并揭示神经元生长和修复的新机制。由于我们的项目采用了独特的化学方法,这项工作可能会揭示用于治疗干预的新蛋白质和途径,并有助于开发新药物以刺激损伤、衰老或疾病后的再生。
公共健康相关性:本研究旨在了解硫酸软骨素糖胺聚糖的结构如何调节基本生物过程,例如蛋白质识别和调节、细胞间通讯、发育和损伤后再生。通过发现这些过程中涉及的新型小分子、蛋白质和途径,这项工作可能最终有助于开发针对多种疾病状态的新治疗方法,例如癌症、传染病和神经退行性疾病。
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)
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Linda C Hsieh-Wilson其他文献
Linda C Hsieh-Wilson的其他文献
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{{ truncateString('Linda C Hsieh-Wilson', 18)}}的其他基金
Expedited Synthesis of Glycosaminoglycans Containing Defined Sulfation Domains
含有特定硫酸化结构域的糖胺聚糖的快速合成
- 批准号:
8985640 - 财政年份:2015
- 资助金额:
$ 39.73万 - 项目类别:
A chemical approach to elucidating the structure-function relationships of chondr
阐明软骨结构与功能关系的化学方法
- 批准号:
8220729 - 财政年份:2010
- 资助金额:
$ 39.73万 - 项目类别:
A chemical approach to elucidating the structure-function relationships of chondronitin sulfate glycosaminoglycans
阐明硫酸软骨素糖胺聚糖结构与功能关系的化学方法
- 批准号:
9134776 - 财政年份:2010
- 资助金额:
$ 39.73万 - 项目类别:
A chemical approach to elucidating the structure-function relationships of chondronitin sulfate glycosaminoglycans
阐明硫酸软骨素糖胺聚糖结构与功能关系的化学方法
- 批准号:
8965476 - 财政年份:2010
- 资助金额:
$ 39.73万 - 项目类别:
A chemical approach to elucidating the structure-function relationships of chondr
阐明软骨结构与功能关系的化学方法
- 批准号:
8423815 - 财政年份:2010
- 资助金额:
$ 39.73万 - 项目类别:
A chemical approach to elucidating the structure-function relationships of chondr
阐明软骨结构与功能关系的化学方法
- 批准号:
8053893 - 财政年份:2010
- 资助金额:
$ 39.73万 - 项目类别:
Role of Fucosyl Saccharides and O-GlcNAc Glycosylation in Neuronal Communication
岩藻糖基糖和 O-GlcNAc 糖基化在神经元通讯中的作用
- 批准号:
7846392 - 财政年份:2009
- 资助金额:
$ 39.73万 - 项目类别:
Role of Fucosyl Saccharides in Neuronal Communication
岩藻糖基糖在神经元通讯中的作用
- 批准号:
6747556 - 财政年份:2003
- 资助金额:
$ 39.73万 - 项目类别:
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