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
• 负责人: Martin D Burke
• 金额: $ 28.7万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8391733
• 关键词: Address; Age related macular degeneration; Antioxidants; Arthritis; Asthma; Atherosclerosis; Attenuated; Biochemical; Biological Factors; Carotene; Carotenoids; Cell membrane; Cells; Chemicals; Clinical; Clinical Trials; Collection; Combinatorial Synthesis; Communities; Complex; Conduct Clinical Trials; Coupling; Development; Diabetes Mellitus; Disease; Employee Strikes; Foundations; Functional disorder; Future; Generations; Goals; Health; Human; In Vitro; Investigation; Knowledge; Lead; Letters; Lipid Bilayers; Lipid Peroxidation; Lipids; Liposomes; Lutein; Macular degeneration; Malignant Neoplasms; Malignant neoplasm of lung; Membrane; Membrane Lipids; Methods; Modification; Neurodegenerative Disorders; Oxygen; Phospholipids; Plants; Polyenes; Preparation; Principal Investigator; Process; Property; Publications; Reactive Oxygen Species; Reperfusion Injury; Research; Rheumatoid Arthritis; Role; Route; Safety; Series; Structure; Structure-Activity Relationship; Testing; Therapeutic Agents; Time; Veins; analog; astaxanthine; base; combinatorial chemistry; design; flexibility; heart disease prevention; high throughput screening; human disease; improved; in vivo; inhibitor/antagonist; interest; lipid peroxidation inhibitor; microorganism; novel; novel therapeutics; oxidative damage; peroxidation; pre-clinical; programs; protective effect; screening; small molecule; zeaxanthin

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

描述（由申请人提供）： 项目摘要 非典型类胡萝卜素的合成：脂质过氧化的自我保护抑制剂 安全有效地抑制脂质双层过氧化的小分子将大大促进许多人类常见疾病的治疗，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 抗脂过氧化物都有重要的局限性。 Me Me O Me H HO Me 例如，典型的类胡萝卜素如 O 虾青素具有强烈的自-Me HO Me peridinin (1) Me OAc 与活性氧 Me 物种破坏性相互作用的倾向，这限制了脂质 O 保护作用的寿命，并导致产生 HO Me Me 有害的类胡萝卜素分解产物。相比之下，最近发现的几种 Me Me Me Me Me OH“非典型”类胡萝卜素具有通过 Me O 聚苯乙烯黄素 (2) 自我保护作用机制发挥卓越抗脂过氧化活性的潜力。 具体来说，该研究计划将开发O高效灵活的合成HO O O O Me非典型类胡萝卜素peridinin (1)、HO O Me synechoxanthin (2)和二-[(6-O-oleoyl-2-D- HO Me Me Me Me glucopyranosyl)oxy]-astaxanthin (3)，进行Me Me Me Me Me系统结构/功能研究，以了解它们的结构和功能。 独特的抗脂过氧化 OH 谱，并通过合理引导的组合合成和高二-[(6-O-油酰基-!-D-吡喃葡萄糖基)氧基]-虾青素 (3) 通量筛选的迭代循环广泛优化其 Me O OH 活性。 PHS 398/2590 (Rev. 05/01) 页面延续格式页面