SYNTHESIS AND BIOCHEMISTRY OF ASCORBIC ACID ANALOGUES

抗坏血酸类似物的合成及生物化学

• 批准号: 2572998
• 负责人: K L KIRK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2572998
• 关键词: ascorbate; biochemistry; biological transport; chemical kinetics; chemical structure function; chemical synthesis; intermolecular interaction; membrane transport proteins; nutrition related tag; transport inhibitor; vitamin analog; vitamin metabolism

Ascorbic acid (vitamin C), a dietary requirement for human health, is an electron donor for several enzymatic actions, functions as an antioxidant, and is implicated in host defense mechanisms, endocrine function and the visual process (lens). Recent renewed interest in the biochemistry of ascorbic acid has been prompted by the realization that relatively little is known concerning the concentrations of the vitamin required for optimum functioning of these several roles. In the case of enzymatic reactions, optimal rate of a process is defined as that concentration that allows the reaction to reach Vmax without toxicity. As part of a program to determine these concentrations, in situ kinetic measurements have been carried out for certain vitamin C- linked reactions. In addition to examination of functional roles of vitamin C, recent characterization of efficient transport mechanisms that translocate vitamin C across cellular membranes has emphasized the importance of the vitamin to biological processes. Kinetic parameters of these transport mechanisms are also being determined. Kinetic measurements of transport inhibition of 6-deoxy-6-haloascorbic acid analogues have clearly demonstrated the presence of separate pathways for the translocation of ascorbic acid and dehydroascorbic acid. Using our route to 6-aryloxy-ascorbic acid analogues, we have prepared radiolabeled functionalized analogues having the potential for irreversible binding to the ascorbic acid transporter. This incluces 6-(4-benzoylphenoxy)-6-deoxyascorbic acid, a potential photoaffinity label. This analogue is transported by the ascorbic acid carrier. To investigate the importance of the 2-hydroxyl group on ascorbic acid activity, we have prepared 2-deoxy-ascorbic acid. This analogue is being used as a starting material for the preparation of the previously unreported 2-deoxy-2-halo ascorbic acids, including 2- deoxy-2-fluoro-ascorbic acid, an isosteric and isopolar, non- oxidizable, analogue.

抗坏血酸（维生素C）是人体健康的膳食必需品， 几种酶促作用的电子供体， 抗氧化剂，并涉及宿主防御机制，内分泌 功能和视觉过程（透镜）。 最近重新对 抗坏血酸的生物化学已经被这一认识所推动 关于这些物质的浓度，我们所知甚少。 维生素所需的最佳功能，这几个角色。 在 在酶促反应的情况下，定义了过程的最佳速率 因为该浓度允许反应达到Vmax， 毒性 作为确定这些浓度的计划的一部分， 已经对某些维生素C进行了原位动力学测量， 关联反应。 除了审查工作人员的职能作用外， 维生素C，高效转运机制的最新表征 维生素C在细胞膜上的转运 维生素对生物过程的重要性。 动力学 这些传输机制的参数也正在确定中。 6-脱氧-6-卤代抗坏血酸转运抑制的动力学测定 酸类似物已经清楚地证明存在单独的 抗坏血酸和脱氢抗坏血酸的转运途径 酸 使用我们的路线6-芳氧基-抗坏血酸类似物，我们有 制备的放射性标记的官能化类似物具有潜在的 用于与抗坏血酸转运蛋白的不可逆结合。 这 包括6-（4-苯甲酰基苯氧基）-6-脱氧抗坏血酸， 光亲和标记 这种类似物是由抗坏血酸 酸载体 探讨2-羟基对抗坏血酸的重要性 酸活性，我们已经制备了2-脱氧抗坏血酸。 该类似物 被用作制备 以前未报道的2-脱氧-2-卤代抗坏血酸，包括2- 脱氧-2-氟-抗坏血酸，一种等排和等极性的，非- 可氧化的类似物。