Multi-Wavelength Fluorescence Radical Dosimetry for Real-Time Assessment of Protein Footprinting Radical Yield
用于实时评估蛋白质足迹自由基产量的多波长荧光自由基剂量测定
基本信息
- 批准号:10250755
- 负责人:
- 金额:$ 25.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAdoptionAmino AcidsAntibodiesAntibody Binding SitesAntineoplastic AgentsAppearanceAwardBehaviorBindingBinding SitesBiological ProcessBiological ProductsBiological Response Modifier TherapyBlood capillariesChemistryComparative StudyDangerousnessDetectionDrug TargetingEnvironmentEpitopesExtracellular ProteinFluorescenceFluorineG-Protein-Coupled ReceptorsGenerationsGoalsGrowth FactorHigher Order Chromatin StructureHumanHydrophobicityHydroxyl RadicalImmune responseIndustryLabelLaboratoriesLasersLeadLettersLigandsLinkMembraneMembrane ProteinsModificationMolecular ConformationMonitorMonoclonal AntibodiesNational Institute of General Medical SciencesNaturePatientsPerformancePharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePhosphotransferasesPlayProcessProductionProtein ConformationProtein FootprintingProteinsProteomeProteomicsReactionReproducibilityResearchRoleSafetySignal TransductionSmall Business Innovation Research GrantSodiumSolventsStructureSurfaceTechniquesTechnologyTimeToxinTransmembrane DomainUniversitiesWashingtonWorkadverse drug reactionanalytical toolaqueousbasedetectordosimetrydruggable targetexperimental studyimprovedinnovationinterestnew technologynovelpathogenpathogenic virusprofessorprogramsresearch and developmenttool
项目摘要
The GenNext Phase I SBIR submssion entitled “Multi-Wavelength Fluorescence
Radical Dosimetry for Real-Time Assessment of Protein Footprinting Radical Yield” is
responsive to the ackowledged need for new and improved tools for higher order
structural analysis (HOS) of biopharmaceuticals and membrane protein target studies.
An emerging HOS analysis technique is hydroxyl radical foot-printing (HRPF). HRPF
involves the irreversible labeling of a protein’s exterior by reaction with hydroxyl radicals
with subsequent MS analysis to identify the outer portions of the protein. We have
developed commercial solutions to perform HRPF. Recently a new and valuable
footprinting technique that relies upon trifluoromethyl (TFM) radicals created by OH
radical attack of aqueous sodium triflinate has been developed that shows great promise
when combined with HRPF. TFM protein footprinting (TFMPF) is highly complementary
to HRPF, as TFMPF effectively labels amino acid residues that are relatively “silent” to
OH radical attack. When used together, HRPF and TFMPF provide substantial coverage
and detection of solvent accessible residues, and as such represent a transformative
improvement to biopharmaceutical HOS assessment.
The practice of TFMPF has been pioneered by Professor Michael Gross of
Washington University, St. Louis, Mo. While showing great promise to address unmet
challenges in pharmaceutical research, reproducibility for TFMPF is challenged by
variability of background scavenging. Collaborating with the Gross laboratory, our work
will extend our innovative HRPF radical dosimetry technology to TFMPF. GenNext
Technologies is the only company commercializing products for HRPF HOS analysis.
Our goal is to convert the combined use of HRPF and TFMPF process from an
academic research experiment into a valuable analytical tool. Once simplified and
transformed into a robust technique, we envision the facile combination of HRPF and
TFMPF to enable: paratope and epitope the interaction of mAb biopharmaceuticals with
their membrane targets; elucidate the dynamics of lead binding to orthosteric or
allosteric membrane targets; to reveal secondary messenger signaling cascades of
GPCR lead compounds; and to detect the impact of orthosteric / allosteric anti-
neoplastics upon targets such as kinases and growth factors.
GenNext Phase I SBIR提交的题为“多波长荧光
用于实时评估蛋白质足迹自由基产率的自由基剂量学”是
对新的和改进的工具的公认的需要作出反应,
生物药物结构分析(HOS)和膜蛋白靶向研究。
一种新兴的HOS分析技术是羟基自由基足迹法(HRPF)。HRPF
涉及通过与羟基自由基反应对蛋白质外部进行不可逆标记
随后进行MS分析以鉴定蛋白质的外部部分。我们有
开发了商业解决方案来执行HRPF。最近一个新的和有价值的
足迹技术,依赖于三氟甲基(TFM)自由基产生的OH
三氟甲磺酸钠水溶液的自由基攻击已被开发,显示出巨大的希望
当与HRPF结合时。TFM蛋白质足迹(TFMPF)是高度互补的
对于HRPF,TFMPF有效地标记相对“沉默”的氨基酸残基,
激进的攻击。如果一起使用,HRPF和TFMPF提供了大量的覆盖面
和溶剂可及残留物的检测,因此代表了一种变革性的
改进生物制药HOS评估。
TFMPF的实践是由Michael Gross教授开创的,
密苏里州圣路易斯市华盛顿大学虽然在解决未实现的问题方面表现出很大的希望,
药物研究面临挑战,TFMPF的重现性受到挑战
背景清除的可变性。与格罗斯实验室合作,我们的工作
将我们创新的HRPF自由基剂量测定技术扩展到TFMPF。GenNext
Technologies是唯一一家将HRPF HOS分析产品商业化的公司。
我们的目标是将HRPF和TFMPF工艺的联合使用从一种
将学术研究实验转化为有价值的分析工具。一旦简化,
转换成一个强大的技术,我们设想的HRPF和
TFMPF使:互补位和表位与mAb生物药物相互作用
它们的膜靶点;阐明铅与正构或
变构膜靶点;揭示第二信使信号级联反应,
GPCR先导化合物;并检测正构/变构抗-
肿瘤的靶点,如激酶和生长因子。
项目成果
期刊论文数量(1)
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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Scot Randy Weinberger其他文献
Scot Randy Weinberger的其他文献
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{{ truncateString('Scot Randy Weinberger', 18)}}的其他基金
Liquid Chromatography Flash Oxidation (LC-Fox™) Protein Footprinting System
液相色谱闪蒸氧化 (LC-Fox™) 蛋白质足迹系统
- 批准号:
10698726 - 财政年份:2023
- 资助金额:
$ 25.14万 - 项目类别:
In-cell Automated Flash Oxidation (IC-AutoFox™) Protein Footprinting System
细胞内自动闪式氧化 (IC-AutoFox™) 蛋白质足迹系统
- 批准号:
10589128 - 财政年份:2020
- 资助金额:
$ 25.14万 - 项目类别:
In-cell Automated Flash Oxidation (IC-AutoFox™) Protein Footprinting System
细胞内自动闪式氧化 (IC-AutoFox™) 蛋白质足迹系统
- 批准号:
10478371 - 财政年份:2020
- 资助金额:
$ 25.14万 - 项目类别:
In-Cell Radical Dosimetry (ICRD) for improved in vivo Fast Photo-oxidation of Proteins Hydroxyl Radical Protein Footprinting
细胞内自由基剂量测定 (ICRD),用于改善蛋白质体内快速光氧化羟基自由基蛋白质足迹
- 批准号:
10009765 - 财政年份:2020
- 资助金额:
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Software for Determining Proteoform Heterogeneity and Protein Expression Fidelity
用于确定蛋白质异质性和蛋白质表达保真度的软件
- 批准号:
10379422 - 财政年份:2019
- 资助金额:
$ 25.14万 - 项目类别:
Software for Determining Proteoform Heterogeneity and Protein Expression Fidelity
用于确定蛋白质异质性和蛋白质表达保真度的软件
- 批准号:
10257385 - 财政年份:2019
- 资助金额:
$ 25.14万 - 项目类别:
Software for Determining Proteoform Heterogeneity and Protein Expression Fidelity
用于确定蛋白质异质性和蛋白质表达保真度的软件
- 批准号:
10582584 - 财政年份:2019
- 资助金额:
$ 25.14万 - 项目类别:
FoxWare™, An Advanced Data Analysis Package for Hydroxyl Radical Foot-Printing Higher Order Structural Analysis
FoxWare™,一种用于羟基自由基足迹高阶结构分析的高级数据分析包
- 批准号:
10092185 - 财政年份:2018
- 资助金额:
$ 25.14万 - 项目类别:
FoxWare™, An Advanced Data Analysis Package for Hydroxyl Radical Foot-Printing Higher Order Structural Analysis
FoxWare™,一种用于羟基自由基足迹高阶结构分析的高级数据分析包
- 批准号:
10334462 - 财政年份:2018
- 资助金额:
$ 25.14万 - 项目类别:
FoxWare™, An Advanced Data Analysis Package for Hydroxyl Radical Foot-Printing Higher Order Structural Analysis
FoxWare™,一种用于羟基自由基足迹高阶结构分析的高级数据分析包
- 批准号:
9907677 - 财政年份:2018
- 资助金额:
$ 25.14万 - 项目类别:
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