CHEMISTRY AND BIOLOGY OF HEPARAN SULFATE
硫酸乙酰肝素的化学和生物学
基本信息
- 批准号:9068299
- 负责人:
- 金额:$ 229.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-23 至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnalytical ChemistryAnimal WelfareAnticoagulantsAreaAwardBiochemicalBiologyBoxingBudgetsBusinessesCell LineCertificationChemistryCitiesClinical TrialsCodeCountryCountyDevelopmentDirect CostsDiseaseDoctor of PhilosophyEconomically Deprived PopulationElectronic MailEmbryoEnzymesFaceFosteringFuture TeacherGlycosaminoglycansGoalsHemostatic functionHeparinHeparin Cofactor IIHeparitin SulfateHuman ResourcesHuman Subject ResearchIn VitroInfectionInflammationInflammation ProcessInflammatoryInstitutesInstructionKnowledgeLaboratoriesLast NameLibrariesLocationMentorsMethodsModelingNIH Program AnnouncementsNamesNeutrophil InfiltrationPharmaceutical ChemistryPhase III Clinical TrialsPolysaccharidesPositioning AttributePrincipal InvestigatorProcessProteinsProvinceRecombinant ProteinsRegistriesRegulationRequest for ApplicationsResearchResearch PersonnelResource DevelopmentResource SharingRoleScientistSepsisServicesSiteSkills DevelopmentSodium ChlorideStructureStudentsSynthesis ChemistryTechnologyTelefacsimileTherapeutic UsesThrombosisTimeUnited States National Institutes of HealthUniversitiesUtahVirginiaWomanXenograft procedureabstractingangiogenesisbiochemical toolsbiophysical toolschemokinecomputational chemistrycomputerized toolscostdesigndrug discoveryhuman embryonic stem cellin vivoin vivo Modelinhibitor/antagonistlung injurynovelperformance siteprofessorprogramsresponseskill acquisitionstemstructural biologytoolxylosides
项目摘要
DESCRIPTION (provided by applicant): This 'The Chemistry and Biology of Heparan Sulfate' proposal is in response to the RFA entitled "Programs of Excellence in Glycosciences (PEG)" (HL-10-026). This PEG consists of four inter-related projects: Project I (Project Leader [PL]: K. Balagurunathan, Univ. of Utah, Salt Lake City, UT) focuses on chemo-enzymatic and 'Click' xyloside-induced synthesis for novel, structurally defined GAGs; Investigating the regulation of HS biosynthetic process and the significance of GAG chain valency; elucidating angiogenesis effects of designed GAGs; and developing inhibitors of HS biosynthetic enzymes to regulate H/HS synthesis in vivo; Project II (PL: U. Desai; Co-Investigators: D. Tollefsen and V. Yadavalli) focuses on elucidating the role of specific and non-specific interactions of H/HS with proteins using computational, biochemical and biophysical technologies; designing specific GAG activators of heparin cofactor II; and developing selected GAGs as clinically useful anticoagulants; Project III (PL: K. Rajarathnam; Co- Investigators: R. Garofalo and J. Iwahara) focuses on understanding the interaction of chemokines with designed H/HS structures using biophysical and structural methods, and developing H/HS structures that modulate neutrophil recruitment process of inflammation occurring in pathological states such as sepsis, lung injury and infection; and Project IV (PL: D. Cooper; Co-Investigators: S. Robson, R. Pierson and A. Azimzadeh) focuses on investigating designed and chemoenzymatically synthesized H/HS agents as anticoagulants in in vitro, ex vivo and in vivo xenotransplantation (xenoTx) models. The central research goals of the PEG utilizes synthetic, computational and analytical chemistry of glycosaminoglycans (GAGs), especially heparin/heparan sulfate (H/HS), to understand their role in modulating hemostasis, thrombosis, inflammation, and angiogenesis, and develop selected agents for use in thrombotic disorders, inflammatory disorders and xenotransplantation. The central skills development goal of the PEG is to mentor three assistant professors, six senior researchers and many other students to be successful glycoscience scientists and mentors. The key resource development goal of this PEG is to develop and make available a library of H/HS structures, computational tools, recombinant proteins, biochemical and biophysical tools and in vitro, ex vivo and in vivo models for GAG studies. This PEG is, thus, a unique, direct and complete effort to discover structurally distinct H/HS for therapeutic use, foster the development of young glycoscience investigators for future faculty positions and establish a shared resource with diverse range of multi-disciplinary glycan research tools. RELEVANCE: This research focuses on synthetic, computational and analytical chemistry of glycosaminoglycans (GAGs), especially heparin/heparan sulfate (H/HS), to understand their role in modulating hemostasis, thrombosis, inflammation, and angiogenesis, and develop selected agents for use in thrombotic and inflammatory disorders, and xenotransplantation. (End of Abstract)
描述(由申请人提供):本“硫酸乙酰肝素的化学和生物学”提案是对标题为“糖科学(PEG)卓越计划”(HL-10-026)的RFA的回应。本PEG由四个相互关联的项目组成:项目I(项目负责人[PL]:K. Balagurunathan,犹他州大学,犹他州盐湖)专注于化学酶法和“点击”木糖苷诱导的新型结构定义的糖胺聚糖合成;研究HS生物合成过程的调节和糖胺聚糖链价的重要性;阐明设计的糖胺聚糖的血管生成作用;开发HS生物合成酶抑制剂以调节体内H/HS合成;项目II(PL:U. Desai; Co-Investigators:D. Tollefsen和V. Yadavalli)专注于使用计算、生物化学和生物物理技术阐明H/HS与蛋白质的特异性和非特异性相互作用的作用;设计肝素辅因子II的特异性GAG活化剂;并开发选择的GAG作为临床有用的抗凝剂;项目III(PL:K. Rajarathnam;共同研究者:R. Garofalo和J. Iwahara)专注于使用生物物理和结构方法理解趋化因子与设计的H/HS结构的相互作用,并开发调节在病理状态如脓毒症、肺损伤和感染中发生的炎症的中性粒细胞募集过程的H/HS结构;和Project IV(PL:D.库珀;合作研究者:S.罗布森河Pierson和A. Azimzadeh)专注于研究设计和化学酶促合成的H/HS试剂在体外、离体和体内异种移植(xenoTx)模型中作为抗凝剂。 PEG的中心研究目标是利用糖胺聚糖(GAG),特别是肝素/硫酸乙酰肝素(H/HS)的合成,计算和分析化学,以了解其在调节止血,血栓形成,炎症和血管生成中的作用,并开发用于血栓性疾病,炎症性疾病和异种移植的选定药物。PEG的核心技能发展目标是指导三名助理教授,六名高级研究人员和许多其他学生成为成功的糖科学家和导师。该PEG的关键资源开发目标是开发和提供H/HS结构库、计算工具、重组蛋白、生物化学和生物物理工具以及用于GAG研究的体外、离体和体内模型。因此,这种PEG是一种独特的,直接的和完整的努力,以发现结构上不同的H/HS用于治疗用途,促进年轻的糖科学研究人员的发展,为未来的教师职位,并建立一个共享的资源与各种多学科的聚糖研究工具。相关性:本研究的重点是糖胺聚糖(GAG),特别是肝素/硫酸乙酰肝素(H/HS)的合成,计算和分析化学,以了解它们在调节止血,血栓形成,炎症和血管生成中的作用,并开发用于血栓形成和炎症性疾病以及异种移植的选定药物。(End摘要)
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(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Umesh Ramanlal Desai其他文献
Umesh Ramanlal Desai的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Umesh Ramanlal Desai', 18)}}的其他基金
Lead identification and pre-clinical studies on allosteric inhibitors of coagulation factor XIa
凝血因子 XIa 变构抑制剂的先导化合物鉴定和临床前研究
- 批准号:
10722847 - 财政年份:2022
- 资助金额:
$ 229.54万 - 项目类别:
Lead identification and pre-clinical studies on allosteric inhibitors of coagulation factor XIa
凝血因子 XIa 变构抑制剂的先导化合物鉴定和临床前研究
- 批准号:
10369394 - 财政年份:2022
- 资助金额:
$ 229.54万 - 项目类别:
Project 3: Role of Glycosaminoglycans in Hematopoiesis
项目3:糖胺聚糖在造血中的作用
- 批准号:
10545019 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Project 3: Role of Glycosaminoglycans in Hematopoiesis
项目3:糖胺聚糖在造血中的作用
- 批准号:
10088970 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Project 3: Role of Glycosaminoglycans in Hematopoiesis
项目3:糖胺聚糖在造血中的作用
- 批准号:
10321582 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Tool for Predicting Glycosaminoglycan Recognition of Proteins
预测蛋白质糖胺聚糖识别的工具
- 批准号:
10062163 - 财政年份:2019
- 资助金额:
$ 229.54万 - 项目类别:
Tool for Predicting Glycosaminoglycan Recognition of Proteins
预测蛋白质糖胺聚糖识别的工具
- 批准号:
10411438 - 财政年份:2019
- 资助金额:
$ 229.54万 - 项目类别:
Tool for Predicting Glycosaminoglycan Recognition of Proteins
预测蛋白质糖胺聚糖识别的工具
- 批准号:
9813586 - 财政年份:2019
- 资助金额:
$ 229.54万 - 项目类别:
Advanced Skills Development in Glyco-Hematology and Glyco-Oncology
糖血液学和糖肿瘤学高级技能发展
- 批准号:
9751362 - 财政年份:2015
- 资助金额:
$ 229.54万 - 项目类别:
Advanced Skills Development in Glyco-Hematology and Glyco-Oncology
糖血液学和糖肿瘤学高级技能发展
- 批准号:
8949552 - 财政年份:2015
- 资助金额:
$ 229.54万 - 项目类别:
相似海外基金
Aquatic Analytical Chemistry
水生分析化学
- 批准号:
CRC-2018-00279 - 财政年份:2022
- 资助金额:
$ 229.54万 - 项目类别:
Canada Research Chairs
Spatially Resolved Analytical Chemistry: Magnetic Resonance and Magnetic Resonance Imaging of Materials and Processes.
空间分辨分析化学:材料和过程的磁共振和磁共振成像。
- 批准号:
RGPIN-2022-04003 - 财政年份:2022
- 资助金额:
$ 229.54万 - 项目类别:
Discovery Grants Program - Individual
Analytical Chemistry of Proteins and Peptides
蛋白质和肽的分析化学
- 批准号:
RGPIN-2020-04677 - 财政年份:2022
- 资助金额:
$ 229.54万 - 项目类别:
Discovery Grants Program - Individual
Spatially Resolved Analytical Chemistry - Magnetic Resonance Imaging of Materials
空间分辨分析化学 - 材料的磁共振成像
- 批准号:
RGPIN-2015-06122 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Discovery Grants Program - Individual
Aquatic Analytical Chemistry
水生分析化学
- 批准号:
CRC-2018-00279 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Canada Research Chairs
Droplet-Based Analytical Chemistry Platforms Using Superhydrophobic and Superamphiphobic Surfaces
使用超疏水和超双疏表面的基于液滴的分析化学平台
- 批准号:
RGPIN-2016-04790 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Discovery Grants Program - Individual
Analytical Chemistry of Proteins and Peptides
蛋白质和肽的分析化学
- 批准号:
RGPIN-2020-04677 - 财政年份:2021
- 资助金额:
$ 229.54万 - 项目类别:
Discovery Grants Program - Individual