ICAM-1 MIMICS AS LFA-1 INHIBITORS
ICAM-1 模拟 LFA-1 抑制剂
基本信息
- 批准号:7960242
- 负责人:
- 金额:$ 9.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AdhesivesAffinityBiologicalBiomedical ResearchBlood VesselsCell AdhesionCollaborationsComputer Retrieval of Information on Scientific Projects DatabaseDataFlow CytometryFluorescenceFundingGrantHemostatic functionHost DefenseInflammationInstitutionIntegrin alpha4beta1IntegrinsIntercellular adhesion molecule 1InvestigationLabelLaboratoriesLeukocytesLigandsManuscriptsMentorsMolecular ConformationNeoplasm MetastasisNew MexicoPathway interactionsPhysiologicalPlayPreparationResearchResearch PersonnelResourcesRoleSignal TransductionSourceUnited States National Institutes of HealthVascular Cell Adhesion Molecule-1analogdesigninhibitor/antagonistinsightinterestsmall molecule
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Background and Specific Aims
Leukocyte integrins play key roles in vascular cell adhesion in host defense, inflammation, hemostasis, and metastasis. Our new data suggest that the affinity of VLA-4 for VCAM-1 can be regulated under special signaling circumstances by distinct physiological pathways. We hypothesize that there is a specific interplay between conformation, applied force, intracellular signaling, and adhesive function. Therefore, small molecule ligands with ability of manipulating the conformational change can be used for elucidating VLA-4 functions.
We propose to pursue the following specific aims:
1) Design and synthesize known VLA-4 inhibitors, which inhibition modes are not clear;
2) Study their biolgical functions in regulating the VLA-4 and related integrins;
3) Design and synthesize new VLA-4 inhibitors.
Results
We have synthesized 3 known potent and selective VLA-4 inhibitors and their fluorescence-labeled analogues. Despite the fact that these compounds have been shown potent and selective inhibitory effect on VLA-4, their inhibition and activation mode are not known. Therefore, the use of these compounds as probes to study the VLA-4 functions, and conformational changes associated with other integrins such as LFA-1 and ICAM-1 is of considerable biological and medicinal significance. With close collaboration with my mentor Sklar and his group, we have conducted studies of VLA-4 and other integrins. Very interesting and important discoveries have been identified (one manuscript in preparation). More detail mechanistic investigations using fluorescent flow cytometry is under way in our laboratories. The mechanistic insights will help us to design more portent and selective VLA-4 inhibitors.
这个子项目是众多研究子项目之一
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)
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WEI WANG其他文献
Pricing and hedging catastrophe equity put options under a Markov-modulated jump diffusion model
马尔可夫调制跳跃扩散模型下的巨灾股票看跌期权的定价和对冲
- DOI:
10.3934/jimo.2015.11.493 - 发表时间:
2014-09 - 期刊:
- 影响因子:1.3
- 作者:
WEI WANG;LINYI QIAN;XIAONAN SU - 通讯作者:
XIAONAN SU
WEI WANG的其他文献
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{{ truncateString('WEI WANG', 18)}}的其他基金
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- 批准号:
9918434 - 财政年份:2019
- 资助金额:
$ 9.65万 - 项目类别:
Design of Fe2+ and H2O2 Induced Proximity Functionalized Imaging Probes for the Control of Cellular Functions
用于控制细胞功能的 Fe2 和 H2O2 诱导接近功能化成像探针的设计
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$ 9.65万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
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9892834 - 财政年份:2018
- 资助金额:
$ 9.65万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
- 批准号:
9918424 - 财政年份:2018
- 资助金额:
$ 9.65万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
- 批准号:
10115754 - 财政年份:2018
- 资助金额:
$ 9.65万 - 项目类别:
A SYSTEMATIC APPROACH TO RECONSTRUCTING TRANSCRIPTION NETWORKS IN THE CELL
重建细胞转录网络的系统方法
- 批准号:
7180239 - 财政年份:2005
- 资助金额:
$ 9.65万 - 项目类别:
Enhanced cardiac sympathetic afferent reflex in CHF
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- 批准号:
6815913 - 财政年份:2004
- 资助金额:
$ 9.65万 - 项目类别:
A SYSTEMATIC APPROACH TO RECONSTRUCTING TRANSCRIPTION
重建转录的系统方法
- 批准号:
6976119 - 财政年份:2004
- 资助金额:
$ 9.65万 - 项目类别:
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