Enhanced Raman Imaging of Ligand-Receptor Recognition
Enhanced Raman Imaging of Ligand-Receptor Recognition
批准号:
10491043
负责人:
Zachary Schultz
金额:
$33.39万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
未结题
起止时间:
2015-04-01 至 2025-08-31
关键词:
AddressAdsorptionAffinityAmino AcidsBindingBinding ProteinsBiochemistryBiologicalBiological AssayCellsChemicalsComplementComplexDetectionDiseaseDrug ScreeningDrug TargetingEnvironmentFailureFluorescence MicroscopyGene MutationGoalsGoldHumanImageImaging ligandsInvestigationLigand BindingLigandsLocationMetalsMethodologyMethodsMicroscopyModelingMolecularMolecular ConformationMonitorOrganismOutcomePeptidesPharmaceutical PreparationsPharmacologic SubstancePhenotypePropertyProteinsRaman Spectrum AnalysisResearchResolutionScanningSerum ProteinsSignal PathwaySignal TransductionSpecificitySurfaceSystemTechniquesTechnologyTherapeuticantagonistbasebiological systemsdrug candidatedrug developmentdrug efficacyexperimental studyimprovedinsightinstrumentationmetallicitymolecular imagingnanoparticlenanoscalenew technologynovel strategiesparticleplasmonicsquantumreceptorreceptor bindingresponseside effectsimulationspectroscopic surveytool
中文摘要
配基-受体识别的增强拉曼成像
摘要:
这项提议的目标是确定与药物靶向和化学物质相关的分子相互作用。
活细胞中的信号。药物开发的一个关键瓶颈是识别非靶点效应。
识别与蛋白质识别和结合药物相关的分子相互作用的方法
细胞和其他活体模型中的候选模型可以用来理解和减少不必要的副作用
和并发症。在药物筛选的早期阶段识别这些影响是重要的,以避免后期
药物失效。我们正在开发利用金属的等离子体性质的技术
纳米颗粒能够对活细胞中的配体-受体结合进行特定的化学光谱研究。这些
研究将为探测与多肽结合的受体的化学残基提供新的方法
拮抗剂,并提供对分子相互作用的见解,这些分子相互作用调节参与信号转导和
药物靶向。
我们的方法结合了两个纳米粒子(表面增强拉曼)的增强拉曼散射
散射(或SERS)和扫描探针(尖端增强拉曼散射,或TERS),纳米粒子跟踪
显微镜,静态和动态量子化学计算的非标准应用,以及超
分辨率SERS成像,以表征调节与蛋白质受体结合的化学相互作用。
增强拉曼散射响应中的信息提供了分子水平的细节
控制蛋白质识别的相互作用。总之,我们的方法论提供了一种新的方法
在活细胞中监测蛋白质与假定药物的结合,并表征靶向特异性。
这项建议的具体目标是:
1)筛选多肽功能化纳米粒在活细胞中的靶向性。
2)开发超分辨率SERS成像以改进结合特异性研究和识别
单元格中的粒子位置。
3)将非标准量子和数值模拟与实验相结合,识别关键
氨基酸构象中与肽结合相关的基序。
总体而言,我们提出的技术和平台将解决获取化学信息的挑战
从配体结合到完整细胞中的受体蛋白。这些研究将为我们提供对
调节信号通路的分子相互作用以及这些相互作用中的异常情况
与疾病和治疗有关。
英文摘要
Enhanced Raman Imaging of Ligand-Receptor Recognition
Abstract:
The goal of this proposal is to identify molecular interactions relevant to drug targeting and chemical
signaling in living cells. A critical bottleneck in the development of drugs is the identification of off-target effects.
Methods that can identify the molecular interactions associated with proteins recognizing and binding to drug
candidates in cellular and other live models can be used to understand and minimize unwanted side effects
and complications. Identifying these effects at earlier stages of drug screening is important to avoid late stage
drug failure. We are developing technologies that take advantage of the plasmonic properties of metallic
nanoparticles to enable chemical-specific spectroscopic studies of ligand-receptor binding in living cells. These
investigations will provide new approaches to probing the receptor’s chemical residues that bind peptide
antagonists and provide insights into molecular interactions that regulate the proteins involved in signaling and
drug targeting.
Our approach combines enhanced Raman scattering from both nanoparticles (Surface enhanced Raman
scattering, or SERS) and scanning probes (tip enhanced Raman scattering, or TERS), nanoparticle tracking
microscopy, non-standard applications of static and dynamic quantum chemical calculations, and super-
resolution SERS imaging to characterize chemical interactions that regulate binding to protein receptors.
Information present in the enhanced Raman scattered response provides molecular level detail of the
interactions governing recognition by the protein. In concert, our methodologies provide a new approach to
monitoring protein binding to putative drugs in living cells, and to characterize targeting specificity.
The specific aims of this proposal are:
1) Screen the targeting specificity of peptide-functionalized nanoparticles in live cells.
2) Develop super-resolution SERS imaging to improve binding specificity studies and identify
particle location in cells.
3) Combine non-standard quantum and numerical simulations with experiments to identify key
motifs in amino acid conformation related to peptide binding.
Overall, the technology and platform we propose will address the challenge of obtaining chemical information
from ligands binding to receptor proteins in intact cells. These studies will provide new insights into the
molecular interactions that regulate signaling pathways and how anomalies in these interactions are
associated with disease and treatment.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Glycosylation Analysis by Sheath-Flow SERS
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批准号:10312126
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项目类别:
-
资助金额:$19.2万
-
财政年份:2021
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负责人:Zachary Schultz
-
依托单位:
Online Raman Diagnostics of Oncometabolites
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批准号:9675692
-
项目类别:
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资助金额:$23.21万
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财政年份:2016
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负责人:Zachary Schultz
-
依托单位:
Online Raman Diagnostics of Oncometabolites
-
批准号:9147682
-
项目类别:
-
资助金额:$36.39万
-
财政年份:2016
-
负责人:Zachary Schultz
-
依托单位:
Enhanced Raman Imaging of Ligand-Receptor Recognition
-
批准号:10687237
-
项目类别:
-
资助金额:$33.35万
-
财政年份:2015
-
负责人:Zachary Schultz
-
依托单位:
Targeted TERS Investigations of Ligand-Receptor Binding
-
批准号:9406141
-
项目类别:
-
资助金额:$3.42万
-
财政年份:2015
-
负责人:Zachary Schultz
-
依托单位:
Enhanced raman imaging of ligand-receptor recognition
-
批准号:10596420
-
项目类别:
-
资助金额:$13.21万
-
财政年份:2015
-
负责人:Zachary Schultz
-
依托单位:
Targeted TERS Investigations of Ligand-Receptor Binding
-
批准号:9211336
-
项目类别:
-
资助金额:$34.2万
-
财政年份:2015
-
负责人:Zachary Schultz
-
依托单位:
Ultrasensitive Label-Free Flow Detector via Surface Enhanced Raman Scattering
-
批准号:8575713
-
项目类别:
-
资助金额:$19.0万
-
财政年份:2013
-
负责人:Zachary Schultz
-
依托单位:
Ultrasensitive Label-Free Flow Detector via Surface Enhanced Raman Scattering
-
批准号:8887351
-
项目类别:
-
资助金额:$19.0万
-
财政年份:2013
-
负责人:Zachary Schultz
-
依托单位:
Ultrasensitive Label-Free Flow Detector via Surface Enhanced Raman Scattering
-
批准号:8729504
-
项目类别:
-
资助金额:$19.0万
-
财政年份:2013
-
负责人:Zachary Schultz
-
依托单位:
Nanoscale Biomembrane Characterization: Model Systems to Cells
-
批准号:8078101
-
项目类别:
-
资助金额:$24.24万
-
财政年份:2009
-
负责人:Zachary Schultz
-
依托单位:
Nanoscale Biomembrane Characterization: Model Systems to Cells
-
批准号:7892504
-
项目类别:
-
资助金额:$24.48万
-
财政年份:2009
-
负责人:Zachary Schultz
-
依托单位:
Nanoscale Biomembrane Characterization: Model Systems to Cells
-
批准号:7810125
-
项目类别:
-
资助金额:$24.89万
-
财政年份:2009
-
负责人:Zachary Schultz
-
依托单位:
海外基金