Development of LED-Assisted NMR Technologies for the Atomic-Resolution Analysis of Medically Relevant Biomolecules in Solution at Submicromolar Concentration
开发 LED 辅助 NMR 技术,对亚微摩尔浓度溶液中的医学相关生物分子进行原子分辨率分析
基本信息
- 批准号:10659378
- 负责人:
- 金额:$ 56.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-08 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAmino AcidsBasic ScienceBuffersCarbonCellsClientCommunitiesData CollectionDependenceDevelopmentDevelopment PlansDevicesDiseaseDyesExhibitsFundingGoalsInvestigationIsotope LabelingLiquid substanceMedicalMethodologyMethodsMolecular ChaperonesMolecular StructureNMR SpectroscopyNational Institute of General Medical SciencesNuclearNuclear Magnetic ResonancePeptidesPhotosensitizing AgentsPhysiologic pulseProtein AnalysisProteinsReportingResearchResolutionSamplingSchemeSolventsSpectrum AnalysisStructureTechnologyTemperatureTestingTimeTryptophanVariantVertebral columnViscosityWorkdetection sensitivityexperimental studyhigh dimensionalityimprovedlight emissionmagnetic fieldmolecular dynamicsnanomolarnew technologynovelrapid detectionsuccesstechnology developmenttool
项目摘要
Project Summary
The goal of this R01 renewal application is to further develop the LED-enhanced NMR technology (LC-photo-
CIDNP) that was established during the prior cycle of funding, and extend the method to the facile and ultra-
rapid 1D-to-3D NMR spectroscopy of proteins at sub-micromolar concentration. We will focus on NMR studies
in solution and will target folded, unfolded and intrinsically disordered proteins in either buffered solution or cell-
like media. We will accomplish the above goals within three steps. First (Specific Aim #1), we will incorporate a
tryptophan (Trp) isotopolog bearing a quasi-isolated 1H-13C spin pair (QISP) within soluble proteins to
achieve unprecedented NMR sensitivity for the detection of solvent-exposed Trp in proteins at nanomolar and
sub-nanomolar levels. We will then employ the above technology in combination with field-cycling to achieve
further NMR sensitivity enhancements. Second (Specific Aim #2) we will extend LC-photo-CIDNP to amino
acids other than Trp and Tyr within proteins. This goal will be accomplished via through-space and through-
bond polarization transfer methodologies. Third (Specific Aim #3), we will extend LC-photo-CIDNP to higher-
dimensionality (>2D) NMR spectroscopy by developing novel 3D (and possibly 4D) 1H,13C heteronuclear
spectroscopy pulse sequences tailored to the analysis of side-chain and backbone 1H-13C resonance pairs.
This effort will include non-uniform-sampling (NUS) data collection schemes. We will then combine theoretical
calculations and experiments to develop better LC-photo-CIDNP dyes with optimized g-factor values and long
photoexcited-state lifetimes, for optimal LC-photo-CIDNP data collection. We will also exploit the peculiar field
dependence of LED-enhanced NMR and implement 2D LC-photo-CIDNP on benchtop NMR spectrometers.
Finally, we will test the success of the improved LC-photo-CIDNP technologies developed in this work by
studying the interaction of an aggregation-prone client protein (SH3 variant) with the Hsp70 molecular
chaperone at sub-micromolar concentration.
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(0)
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Silvia Cavagnero其他文献
Silvia Cavagnero的其他文献
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{{ truncateString('Silvia Cavagnero', 18)}}的其他基金
Development of a Laser-Assisted NMR Technology for the Atomic-Resolution Analysis of Medically Relevant Biomolecules in Solution at Submicromolar Concentration
开发激光辅助核磁共振技术,对亚微摩尔浓度溶液中医学相关生物分子进行原子分辨率分析
- 批准号:
10020189 - 财政年份:2018
- 资助金额:
$ 56.9万 - 项目类别:
Development of a Laser-Assisted NMR Technology for the Atomic-Resolution Analysis of Medically Relevant Biomolecules in Solution at Submicromolar Concentration
开发激光辅助核磁共振技术,对亚微摩尔浓度溶液中医学相关生物分子进行原子分辨率分析
- 批准号:
10242819 - 财政年份:2018
- 资助金额:
$ 56.9万 - 项目类别:
Development of Laser-Mediated Hyper-Sensitive NMR in Liquids
激光介导液体超灵敏核磁共振的发展
- 批准号:
8757756 - 财政年份:2014
- 资助金额:
$ 56.9万 - 项目类别:
Development of Laser-Mediated Hyper-Sensitive NMR in Liquids
激光介导液体超灵敏核磁共振的发展
- 批准号:
8898152 - 财政年份:2014
- 资助金额:
$ 56.9万 - 项目类别:
Analysis of De Novo Protein Folding by Fluorescence Resonance Energy Transfer
通过荧光共振能量转移分析从头蛋白质折叠
- 批准号:
8373308 - 财政年份:2012
- 资助金额:
$ 56.9万 - 项目类别:
Analysis of De Novo Protein Folding by Fluorescence Resonance Energy Transfer
通过荧光共振能量转移分析从头蛋白质折叠
- 批准号:
8550099 - 财政年份:2012
- 资助金额:
$ 56.9万 - 项目类别:
Analysis of De Novo Protein Folding by Fluorescence Resonance Energy Transfer
通过荧光共振能量转移分析从头蛋白质折叠
- 批准号:
8852633 - 财政年份:2012
- 资助金额:
$ 56.9万 - 项目类别:
Analysis of De Novo Protein Folding by Fluorescence Resonance Energy Transfer
通过荧光共振能量转移分析从头蛋白质折叠
- 批准号:
8668100 - 财政年份:2012
- 资助金额:
$ 56.9万 - 项目类别:
CONFORMATION OF HSP70-BOUND PEPTIDE SUBSTRATES PROBED USING NMR SPECTROSCOPY
使用核磁共振波谱探测 HSP70 结合肽底物的构象
- 批准号:
8361245 - 财政年份:2011
- 资助金额:
$ 56.9万 - 项目类别:
Ultra-sensitive NMR via Photochemically induced dynamic nuclear polarization
通过光化学诱导动态核极化的超灵敏核磁共振
- 批准号:
7991252 - 财政年份:2010
- 资助金额:
$ 56.9万 - 项目类别:
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