Development of Bifunctional and Light Activated ReACT Bioconjugation Reagents via Nitrone Photoisomerization
通过硝酮光异构化开发双功能光激活 ReACT 生物共轭试剂
基本信息
- 批准号:10555205
- 负责人:
- 金额:$ 6.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesBiocompatible MaterialsBiologicalChemical StructureChemicalsChemistryClinicalCross-Linking ReagentsDevelopmentERBB2 geneElectronicsImmunotherapyIn SituIsomerismLabelLaboratoriesLibrariesLigationLightMethionineMethodologyMethodsOrganic SynthesisOxidation-ReductionPhotochemistryPost-Translational Protein ProcessingProteinsReactionReagentRegression AnalysisResearchResearch PersonnelRouteSamplingStructureSulfurTherapeuticTimeTrainingabsorptionchemical stabilitycrosslinkexperiencefunctional groupmethod developmentnitronenoveloxaziridineoxidationskill acquisitionskillsspatiotemporaltool
项目摘要
PROJECT SUMMARY/ABSTRACT
The unique reactivity of oxaziridines towards methionine sidechains via N-transfer has been
successfully leveraged to make powerful bioconjugation reagents used by numerous research groups.
However, the utility of this reagent is limited by the difficulty of incorporating secondary reactive
handles and a narrow cargo scope due to the harsh synthesis conditions and sensitivity of oxaziridines.
Photoisomerization of nitrones provides a mild method of oxaziridine synthesis. This route to
oxaziridines allows for incorporation of cargo not accessible with current synthetic methods and
presents a powerful way of controlling oxaziridine reactivity using light. This proposal aims to elucidate
quantitative relationships between nitrone chemical structure and its ability to isomerize to
oxaziridines and the resulting oxaziridine bioconjugation reactivity. Nitrone photoisomerization will be
leveraged to synthesize bivalent reagents that incorporate other commonly used click handles. Finally,
the exquisite control over oxaziridine reactivity provided by the photoisomerization will be used to
uncage oxaziridine reactivity in situ for protein modifications. These studies will greatly expand the
utility of this valuable class of bioconjugation reagents.
项目总结/摘要
已经研究了氧氮杂环丙烷通过N-转移对甲硫氨酸侧链的独特反应性。
成功地利用它来制造许多研究小组使用的强大的生物缀合试剂。
然而,该试剂的实用性受到难以引入次级反应性的限制。
由于合成条件苛刻和氧氮杂环丙烷的敏感性,
硝酮的光异构化反应为氧氮丙啶的合成提供了一种温和的方法。这条货运路线来
氧氮杂环丙烷允许掺入用目前的合成方法无法获得的货物,
提出了一种利用光控制氧氮丙啶反应性的有效方法。这项建议旨在阐明
硝酮化学结构与其异构化能力之间的定量关系,
氧氮丙啶和所得氧氮丙啶生物缀合反应性。硝酮光异构化将是
用于合成掺入其它常用点击柄的二价试剂。最后,
对光异构化提供的氧氮丙啶反应性的精确控制将用于
用于蛋白质修饰的原位释放氧氮丙啶反应性。这些研究将大大扩展
这类有价值的生物缀合试剂的实用性。
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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{{ truncateString('Kacper Skakuj', 18)}}的其他基金
Development of Bifunctional and Light Activated ReACT Bioconjugation Reagents via Nitrone Photoisomerization
通过硝酮光异构化开发双功能光激活 ReACT 生物共轭试剂
- 批准号:
10389513 - 财政年份:2022
- 资助金额:
$ 6.95万 - 项目类别:
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