Engineered probes for sialoglycan detection
用于唾液酸聚糖检测的工程探针
基本信息
- 批准号:10266164
- 负责人:
- 金额:$ 45.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-20 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdhesivesAffinityAntibodiesAntigensArthritisAutoimmune DiseasesAutoimmunityBacterial AdhesinsBacterial Attachment SiteBacterial InfectionsBindingBinding ProteinsBiologicalBiological AssayBlood specimenCancer PatientCellsCrystallizationDetectionDevelopmentDiagnosticDiagnostic Reagent KitsDisaccharidesDiseaseDisease OutbreaksEngineeringEnzymesGlycolsGlycoproteinsHarvestHumanLaboratoriesLectinLettersLibrariesLigandsLinkMalignant NeoplasmsMass Spectrum AnalysisMeasuresMediatingMedicalMethodsModificationOutcomePlasmaPolysaccharidesPositioning AttributeProcessPropertyProtein EngineeringProteinsReagentResolutionRoleSARS coronavirusSamplingSevere Acute Respiratory SyndromeSialic AcidsSialyltransferasesSignal TransductionSpecificityStainsStreptococcus adhesinStructureTechniquesTimeTn antigenTrisaccharidesVirus DiseasesWorkbasecancer biomarkerscancer typecoronavirus receptorexperimental studyglycosylationinstrumentationpreferencereceptorscaffoldsialic acid binding Ig-like lectintool
项目摘要
PROJECT SUMMARY/ABSTRACT
Sialoglycans can be poor antigens, meaning that it can be challenging to develop effective antibodies for
their detection. Instead, sialoglycan mapping heavily relies upon mass spectrometry, which requires expertise
and instrumentation available to few laboratories. One recent push in the field has been to harvest the breadth
of selectivity found within naturally-occurring sialoglycan-binding proteins in order to develop glycan-detecting
proteins. This strategy identified a number of sialoglycan-binding proteins, particularly those that bind with high
affinity and narrow selectivity to sialyl-T antigen (sTa). However, major gaps remain in the spectrum of the
sialoglycans that are recognized.
Here, we focus on sialoglycans that are likely abundant on cells or that are prevalent in disease but that lack
practical probes for their detection, specifically α2,3 linked and α2,6 linked sialoglycans. We propose to create
probes that recognize these glycans by tailoring the specificity of existing sialoglycan binding proteins using
structure-based protein engineering.
In Aim 1, we engineer the bacterial Siglec-like adhesins to create a library of probes for tri- and tetra-
saccharides, each of which binds one α2,3 linked sialoglycan with high affinity and narrow selectivity.
In Aim 2, we apply engineering principles to the development of probes for α2,3 linked sialoglycans and
focus on the α2,6 linked sialyl Tn antigen disaccharide, a biomarker for cancer.
In Aim 3, we evaluate the utility of these probes in measuring glycans in human plasma, and cross-validated
these by affinity capture and mass spectrometry. The ability to distinguish glycan abundance and repertoire in
healthy donors versus cancer patients will be included as a part of this aim. Successful probes will be distributed
for use both in lectin arrays and in low-throughput assays.
项目总结/文摘
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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T M Iverson其他文献
T M Iverson的其他文献
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{{ truncateString('T M Iverson', 18)}}的其他基金
Molecular basis for arrestin-mediated signaling
抑制蛋白介导的信号传导的分子基础
- 批准号:
9324338 - 财政年份:2016
- 资助金额:
$ 45.19万 - 项目类别:
Mechanisms for ligand binding by serine-rich adhesins of Gram-positive pathogens
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8788229 - 财政年份:2014
- 资助金额:
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STRUCTURAL STUDIES OF TRANSMEMBRANE SIGNALING COMPLEXES AND NOVEL THERAPEUTIC AG
跨膜信号复合物和 NOVEL THERAPEUTIC AG 的结构研究
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8362282 - 财政年份:2011
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$ 45.19万 - 项目类别:
Stabilization of Membrane Protein Signaling Complexes
膜蛋白信号复合物的稳定性
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8310115 - 财政年份:2010
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$ 45.19万 - 项目类别:
Stabilization of Membrane Protein Signaling Complexes
膜蛋白信号复合物的稳定性
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8519131 - 财政年份:2010
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$ 45.19万 - 项目类别:
STRUCTURAL STUDIES OF TRANSMEMBRANE SIGNALING COMPLEXES AND NOVEL THERAPEUTIC AG
跨膜信号复合物和 NOVEL THERAPEUTIC AG 的结构研究
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8170283 - 财政年份:2010
- 资助金额:
$ 45.19万 - 项目类别:
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