Identification of Flavonoid Metabolites
类黄酮代谢物的鉴定
基本信息
- 批准号:7660907
- 负责人:
- 金额:$ 7.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2011-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAntioxidantsAreaAtherosclerosisAwarenessBiological AvailabilityBiological MarkersBody FluidsCarcinogensCategoriesCellsChemopreventionChemopreventive AgentCitrusCitrus FruitComplexConsumptionDNA DamageDevelopmentDietary ComponentDietary intakeDivision of Cancer PreventionDrug KineticsEarly DiagnosisEnzymesEpidemiologic StudiesExhibitsFlavanonesFlavonoidsFoodFoundationsFree RadicalsFutureGlucuronidesGlycosidesGrantHealth BenefitHeart DiseasesHepaticHumanHydrolysisInflammationInorganic SulfatesIsomerismMapsMass Spectrum AnalysisMeasuresMetabolic BiotransformationMetalsMethodologyMethodsMonitorNIH Program AnnouncementsNational Cancer InstituteNutrientOutcomeParentsPhysiologicalPhytochemicalPlantsPlasmaPrevention ResearchPropertyReportingResearchSiteSpecificityTechniquesTissuesTumor PromotionUnspecified or Sulfate Ion SulfatesUrineVariantWorkanalytical methodanalytical toolcancer preventionchemical standardfallsflavanonefruits and vegetablesglycosylationhesperetininnovationnutritionprogramsresponsestemsuccesssugartandem mass spectrometrytumoruptake
项目摘要
DESCRIPTION (provided by applicant):
Flavonoids are a broad class of phenolic phytochemicals that exhibit chemopreventive properties in humans. Extensive evidence suggests that flavonoids display antitumor activities, in terms of protection against DNA damage by neutralization of free radicals and inhibition of tumor development via modulation of hepatic enzymes involved in activation/deactivation of carcinogens. It is generally accepted that flavonoids are hydrolyzed to aglycones upon consumption, then biotransformed to other species. The resulting aglycones and metabolites may be absorbed to different extents and exert different physiological activities, thus making the mapping of pharmacokinetics and bioavailability a complex problem. Moreover, analytical methods to identify flavonoid metabolites have lacked the specificity to detect low levels in plasma, urine, tissues, and cells, as well as suffering from lack of chemical standards necessary to validate methods and allow accurate quantitation. This proposal is aimed directly at addressing these problems via: (i) enzymatic synthesis of flavonoid biotransformation products. We will use commercially available enzymes to produce glucuronides and sulfates from parent flavonoid aglycones. (ii) metal complexation strategies/tandem mass spectrometry: We will develop innovative metal complexation methods, for which we have had outstanding success in recent years, with tandem mass spectrometry for structural characterization of the resulting flavonoid metabolites and for isomer differentiation. The most important outcomes of the proposed work are twofold: 1) the first comprehensive analysis of flavonoid metabolites, and 2) the development of sensitive analytical tools for identification of flavonoid metabolites. This work will provide archival mass spectra of numerous flavonoid metabolites plus validated mass spectrometric methodology, and ultimately afford tremendous inroads for subsequent bioavailability, uptake, distribution, and pharmacokinetic studies of flavonoids.
描述(由申请人提供):
黄酮类化合物是一类广泛的酚类植物化学物质,在人类中表现出化学预防特性。大量的证据表明,黄酮类化合物显示抗肿瘤活性,在保护免受DNA损伤的自由基中和和抑制肿瘤的发展,通过调节参与激活/灭活致癌物的肝酶。人们普遍认为,类黄酮在食用时水解为糖苷配基,然后生物转化为其他物种。由此产生的糖苷配基和代谢产物可能被吸收到不同的程度,并发挥不同的生理活性,从而使药代动力学和生物利用度的映射成为一个复杂的问题。此外,鉴定类黄酮代谢物的分析方法缺乏检测血浆、尿液、组织和细胞中低水平的特异性,并且缺乏验证方法和允许准确定量所需的化学标准。该提议直接旨在通过以下方式解决这些问题:(i)类黄酮生物转化产物的酶促合成。我们将使用市售的酶从母体黄酮苷元中生产葡萄糖醛酸苷和硫酸盐。(ii)金属络合策略/串联质谱:我们将开发创新的金属络合方法,近年来我们在这方面取得了巨大的成功,串联质谱用于所产生的黄酮代谢物的结构表征和异构体区分。最重要的成果是两方面的:1)第一次全面分析类黄酮代谢物,2)开发灵敏的分析工具,用于鉴定类黄酮代谢物。这项工作将提供大量类黄酮代谢物的档案质谱加上验证的质谱方法,并最终为后续的生物利用度,摄取,分布和类黄酮的药代动力学研究提供巨大的进展。
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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Jennifer S. Brodbelt其他文献
Effects of functional group interactions on the bimolecular and dissociation reactions of diols
- DOI:
10.1016/1044-0305(92)85030-n - 发表时间:
1992-07-01 - 期刊:
- 影响因子:
- 作者:
Erika S. Eichmann;Erwin Alvarez;Jennifer S. Brodbelt - 通讯作者:
Jennifer S. Brodbelt
Evaluation of steric and substituent effects in phenols by competitive reactions of dimethyl ether ions in a quadrupole ion trap
- DOI:
10.1016/s1044-0305(05)80051-0 - 发表时间:
1995-08-01 - 期刊:
- 影响因子:
- 作者:
Gerald F. Bauerle;Jennifer S. Brodbelt - 通讯作者:
Jennifer S. Brodbelt
Tracking molecular mobility
追踪分子迁移率
- DOI:
10.1038/nchem.382 - 发表时间:
2009-10-01 - 期刊:
- 影响因子:20.200
- 作者:
Jennifer S. Brodbelt - 通讯作者:
Jennifer S. Brodbelt
Ultraviolet photoactivation perturbs the metal-ligand interface of atomically precise nanoclusters
紫外光活化干扰了原子精确纳米团簇的金属-配体界面
- DOI:
10.1039/d5cc00757g - 发表时间:
2025-03-27 - 期刊:
- 影响因子:4.200
- 作者:
Anagha Jose;Jada N. Walker;Maya Khatun;Sami Malola;B. S. Sooraj;Hannu Häkkinen;Jennifer S. Brodbelt;Thalappil Pradeep - 通讯作者:
Thalappil Pradeep
Correlation between Spectroscopic and Structural Features of Dimeric DNA-Templated Silver Nanoclusters using Mass Spectrometry
- DOI:
10.1016/j.bpj.2020.11.1731 - 发表时间:
2021-02-12 - 期刊:
- 影响因子:
- 作者:
Soonwoo Hong;Ines C. Santos;Yu-An Kuo;Yuan-I Chen;Trung D. Nguyen;Hsin-Chin Li;Pranav Anbarasu;Jennifer S. Brodbelt;Tim Yeh - 通讯作者:
Tim Yeh
Jennifer S. Brodbelt的其他文献
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{{ truncateString('Jennifer S. Brodbelt', 18)}}的其他基金
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
- 批准号:
10418608 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
- 批准号:
10620850 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
- 批准号:
10320024 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
- 批准号:
10389836 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
- 批准号:
10089703 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
- 批准号:
10797256 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
- 批准号:
10543449 - 财政年份:2021
- 资助金额:
$ 7.08万 - 项目类别:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
真核转录过程中RNA聚合酶II磷酸化密码的解读
- 批准号:
9751900 - 财政年份:2018
- 资助金额:
$ 7.08万 - 项目类别:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
真核转录过程中RNA聚合酶II磷酸化密码的解读
- 批准号:
10158496 - 财政年份:2018
- 资助金额:
$ 7.08万 - 项目类别:
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