Para-hydrogen induced polarization of 13C labeled TCA cycle metabolite precursors
13C 标记的 TCA 循环代谢物前体的仲氢诱导极化
基本信息
- 批准号:10434648
- 负责人:
- 金额:$ 24.6万
- 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:2021-08-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAcidsBolus InfusionCarbonCell NucleusChemicalsChemistryCitric Acid CycleDevelopmentElectron TransportFormulationFree RadicalsGasesGoalsHourHydrogenHydrogenationIndividualInjectionsIsomerismL FormsLabelLiquid substanceLiverMagnetic Resonance ImagingMalatesMetabolicMetabolismMolecularMusN-methylacetamide-oxotremorine MNatureNuclearOpticsOrangesOxaloacetatesPositioning AttributePositron-Emission TomographyProtein IsoformsPyruvateRelaxationSamplingSeriesSignal TransductionSystemTechniquesTemperatureTestingTimeWorkalpha ketoglutaratecatalystchemical additioncold temperaturecost effectivecryogenicsenolenolatein vivoinnovationlarge scale productionmagnetic fieldmetabolic abnormality assessmentmicrowave electromagnetic radiationnoveloperationpi bondpressureprospectivescale upvirtual
项目摘要
Abstract
In vivo 13C MRS/MRI offers the unique opportunity to observe various metabolic processes in real time as they
happen when enabled by a hyperpolarization technique. The most common technique for hyperpolarization is
dissolution Dynamic Nuclear Polarization (DNP). DNP works by enhancing the NMR signal via the microwave-
driven polarization transfer from electrons to target nuclei. While dissolution DNP-NMR can produce dramatically
enhanced liquid state NMR signals, it has severe limitations including expensive hardware, the need for a free
radical polarizing agent, extended polarization build-up time at cryogenic temperatures and batch-wise operation.
An alternative technique for 13C hyperpolarization is para-hydrogen induced polarization (PHIP), which involves
the chemical addition of para-hydrogen (hydrogen gas enriched in the para spin isomer) to unsaturated
substrates followed by the conversion of the singlet spin order of the para-H2 into 13C spin polarization by
magnetic field cycling. Although PHIP requires specific chemistry, the advantages of PHIP over DNP make this
technique very appealing: it is far less expensive, faster and capable of the large-scale production of
hyperpolarized samples, potentially in a continuous flow manner. In this exploratory project we will develop
innovative chemistries (13C-enriched, unsaturated precursors to important metabolites and novel catalyst
systems) that will significantly widen the scope of PHIP for 13C metabolic studies. The goal of Aim 1 is the
synthesis and PHIP of 13C-labeled, unsaturated precursors to 2-ketoglutarate, an important intermediate of the
TCA cycle. In Aim 2, we will explore the PHIP of O-acetylated enol derivatives of 13C labeled pyruvate and
oxaloacetate. Catalytic hydrogenation of these intermediates will yield lactate and malate derivatives. A major
goal of this aim will be the development of chiral catalyst systems that would preferentially afford the natural L-
form of these important metabolites.
摘要
在体内13 C MRS/MRI提供了独特的机会,观察各种代谢过程中的真实的时间,因为他们
发生时,启用超极化技术。最常用的超极化技术是
溶解动态核极化(DNP)。DNP的工作原理是通过微波增强NMR信号-
从电子到靶核的驱动极化转移。而溶解DNP-NMR可以产生显着的
增强的液态NMR信号,它有严重的限制,包括昂贵的硬件,需要免费的
自由基极化剂,在低温下延长的极化建立时间和分批操作。
用于13 C超极化的替代技术是仲氢诱导极化(PHIP),其涉及
将仲氢(富含帕拉自旋异构体的氢气)化学加成到不饱和的
衬底,然后通过以下步骤将对-H2的单重态自旋顺序转化为13 C自旋极化:
磁场循环虽然PHIP需要特定的化学反应,但PHIP相对于DNP的优势使其
技术非常有吸引力:它是更便宜,更快,能够大规模生产的
超极化的样品,可能以连续流动的方式。在这个探索性的项目中,我们将开发
创新化学(富含13 C的重要代谢物和新型催化剂的不饱和前体
系统),这将显着扩大PHIP的13 C代谢研究的范围。目标1的目标是
合成和PHIP的13 C标记的,不饱和的前体2-酮戊二酸,一个重要的中间体,
TCA循环。在目标2中,我们将探索13 C标记的丙酮酸的O-乙酰化烯醇衍生物的PHIP,
草酰乙酸。这些中间体的催化氢化将产生乳酸盐和苹果酸盐衍生物。一个主要
这一目标的目标将是开发优先提供天然L-
这些重要的代谢物的形式。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo.
- DOI:10.3390/molecules27010058
- 发表时间:2021-12-23
- 期刊:
- 影响因子:0
- 作者:Do QN;Lenkinski RE;Tircso G;Kovacs Z
- 通讯作者:Kovacs Z
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Zoltan Kovacs其他文献
Zoltan Kovacs的其他文献
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{{ truncateString('Zoltan Kovacs', 18)}}的其他基金
Hyperpolarized 13C probes for the one carbon metabolism
用于一碳代谢的超极化 13C 探针
- 批准号:
10647293 - 财政年份:2023
- 资助金额:
$ 24.6万 - 项目类别:
Hyperpolarized 89Y complexes as potential in vivo imaging agents
超极化 89Y 复合物作为潜在的体内成像剂
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7573139 - 财政年份:2009
- 资助金额:
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Hyperpolarized 89Y complexes as potential in vivo imaging agents
超极化 89Y 复合物作为潜在的体内成像剂
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7802862 - 财政年份:2009
- 资助金额:
$ 24.6万 - 项目类别:
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