Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati
非典型类胡萝卜素的合成:脂质过氧化物的自我保护抑制剂
基本信息
- 批准号:7767348
- 负责人:
- 金额:$ 30.07万
- 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:2009-12-01 至 2013-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAgeAge related macular degenerationAntioxidantsArthritisArtsAsthmaAtherosclerosisAttenuatedBiochemicalBiological FactorsCaroteneCarotenoidsCell membraneCellsChemicalsClinical TrialsCollectionCombinatorial SynthesisCommunitiesComplexConduct Clinical TrialsCouplingDevelopmentDiabetes MellitusDiseaseEmployee StrikesFigs - dietaryFoundationsFunctional disorderFutureGenerationsGoalsHandHealthHumanIn VitroInvestigationKnowledgeLeadLettersLipid BilayersLipid PeroxidationLipidsLiposomesLuteinMacular degenerationMalignant NeoplasmsMalignant neoplasm of lungMembraneMembrane LipidsMethodsModificationNeurodegenerative DisordersOxygenPhospholipidsPlantsPolyenesPreparationPrincipal InvestigatorProcessPropertyPublicationsReactive Oxygen SpeciesReperfusion InjuryResearchRheumatoid ArthritisRoleRouteSafetyScreening procedureSeriesStructureStructure-Activity RelationshipTestingTherapeutic AgentsTimeVeinsanalogastaxanthinebaseclinical effectcombinatorial chemistrydesignflexibilityheart disease preventionhigh throughput screeninghuman diseaseimprovedin vivoinhibitor/antagonistinterestlipid peroxidation inhibitormicroorganismnovelnovel therapeuticsoxidative damageperoxidationpre-clinicalprogramsprotective effectpublic health relevancesmall moleculezeaxanthin
项目摘要
DESCRIPTION (provided by applicant): Project Summary Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidation Small molecules that safely and effectively inhibit the peroxidation of lipid bilayers stand to substantially advance the treatment of many prevalent human diseases, including atherosclerosis, cancer, macular degeneration, and arthritis. However, most of the known O antilipoperoxidants have important limitations. Me Me O Me H HO Me For example, typical carotenoids such as O astaxanthin have a strong propensity for self- Me HO Me peridinin (1) Me OAc destructive interactions with reactive oxygen Me species, which limits the lifetime of the lipid O protective effect and leads to the generation of HO Me Me harmful carotenoid breakdown products. In contrast, there are several recently discovered Me Me Me Me OH "atypical" carotenoids that have the potential Me for exceptional antilipoperoxidant activities via Me O synechoxanthin (2) self-preserving mechanisms of action. Specifically, this research program will develop O highly efficient and flexible syntheses of the HO O O O Me atypical carotenoids peridinin (1), HO O Me synechoxanthin (2), and di-[(6-O-oleoyl-2-D- HO Me Me Me Me glucopyranosyl)oxy]-astaxanthin (3), execute Me Me Me Me systematic structure/function studies to Me O O OO OH understand their unique antilipoperoxidant OH profiles, and extensively optimize their Me O OH activities via iterative cycles of rationally- guided combinatorial synthesis and high- di-[(6-O-oleoyl-!-D-glucopyranosyl)oxy]-astaxanthin (3) throughput screening. PHS 398/2590 (Rev. 05/01) Page Continuation Format Page
PUBLIC HEALTH RELEVANCE: Project Narrative Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidation Several recently discovered natural products have the potential to serve as powerful antioxidants inside cell membranes, and therefore may lead to improved treatments for a variety of prevalent diseases, including atherosclerosis, cancer, and arthritis. In contrast to related antioxidants that have been studied previously, these new compounds do not self-destruct as they protect the membrane from oxidative damage, which is critical for maximizing efficacy and safety. This research program will lead to the efficient synthesis, detailed study, and extensive optimization of these novel "self-preserving" antioxidants. PHS 398/2590 (Rev. 05/01) Page Continuation Format Page
非典型类胡萝卜素的合成:自我保存的脂质过氧化抑制剂安全有效地抑制脂质双分子层过氧化的小分子有望极大地推进许多常见人类疾病的治疗,包括动脉粥样硬化、癌症、黄斑变性和关节炎。然而,大多数已知的O型抗脂过氧化剂都有重要的局限性。例如,典型的类胡萝卜素如O虾青素具有很强的自我Me HO Me peridinin (1) Me OAc与活性氧Me的破坏性相互作用倾向,这限制了脂质O保护作用的寿命,导致产生HO Me Me有害的类胡萝卜素分解产物。相比之下,最近发现了几种Me Me Me Me Me OH“非典型”类胡萝卜素,它们通过Me O协同黄质(2)自我保护机制具有特殊的抗脂质过氧化活性。具体地说,这个研究项目将开发的高效和灵活的合成HO O O O我非典型类胡萝卜素peridinin(1),何鸿燊O我synechoxanthin(2),和di - [(6-O-oleoyl-2-D - HO我我我我glucopyranosyl)氧)虾青素(3),执行我我我我我系统的结构/功能研究O O OO哦了解他们独特的antilipoperoxidant概要文件,并通过合理引导的组合合成和高二-[(6-O-油基-)]的迭代循环广泛优化其Me O OH活性。- d -葡萄糖吡喃基氧[-虾青素(3)通量筛选。小灵通398/2590 (Rev. 05/01)页延续格式页
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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Martin D Burke其他文献
Flexible tetracycline synthesis yields promising antibiotics
灵活的四环素合成产生有前途的抗生素
- DOI:
10.1038/nchembio0209-77 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:13.700
- 作者:
Martin D Burke - 通讯作者:
Martin D Burke
Martin D Burke的其他文献
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{{ truncateString('Martin D Burke', 18)}}的其他基金
Using a small molecule iron transporter to understand and treat FPN1 deficiencies in mice
使用小分子铁转运蛋白来了解和治疗小鼠 FPN1 缺陷
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10181021 - 财政年份:2018
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$ 30.07万 - 项目类别:
Using a small molecule iron transporter to understand and treat FPN1 deficiencies in mice
使用小分子铁转运蛋白来了解和治疗小鼠 FPN1 缺陷
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Synthesis and Study of Amphotericin B Derivatives
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7929731 - 财政年份:2009
- 资助金额:
$ 30.07万 - 项目类别:
Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati
非典型类胡萝卜素的合成:脂质过氧化物的自我保护抑制剂
- 批准号:
8391733 - 财政年份:2009
- 资助金额:
$ 30.07万 - 项目类别:
Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati
非典型类胡萝卜素的合成:脂质过氧化物的自我保护抑制剂
- 批准号:
7993589 - 财政年份:2009
- 资助金额:
$ 30.07万 - 项目类别:
Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati
非典型类胡萝卜素的合成:脂质过氧化物的自我保护抑制剂
- 批准号:
8197629 - 财政年份:2009
- 资助金额:
$ 30.07万 - 项目类别:
Synthesis and Study of Amphotericin B Derivatives
两性霉素B衍生物的合成与研究
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8505913 - 财政年份:2007
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$ 30.07万 - 项目类别:
Synthesis and Study of Amphotericin B Derivatives
两性霉素B衍生物的合成与研究
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$ 30.07万 - 项目类别:
Synthesis and Study of Amphotericin B Derivatives
两性霉素B衍生物的合成与研究
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7563730 - 财政年份:2007
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$ 30.07万 - 项目类别:
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