SYNTHETIC ANALOGS OF FRUCTOSE PHOSPHATES AND RIBOSIDES

果糖磷酸酯和核糖苷的合成类似物

• 批准号: 3234051
• 负责人: CRAIG S WILCOX
• 金额: $ 12万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234051
• 关键词: 6 phosphofructokinase; O glycosidase; adenosine monophosphate; adenosine triphosphate; carbopolycyclic compound; chemical synthesis; enzyme induction /repression; fructose phosphate; glucagon; glucose; glycosides; ribose phosphate; riboside

The main objective of this project is the synthesis of a carbocyclic analog of the important metabolic regulator 2,6-diphosphofructose. This molecule is the strongest known positive effector of the enzyme 6-phosphofructokinase which catalyzes a key control step in the breakdown of glucose or glucagon to provide ATP. The carbocyclic analog is hypothesized to be much more stable than the parent regulator and may well be inert to an enzyme which normally hydrolyzes 2,6-diphosphofructose, 2,6-diphosphofructo-2-phosphatase (FBPase 2). The availability of this analog will allow several interesting experiments to be carried out and these experiments will lead to an increased understanding of the reactions catalyzed by phosphofructokinase and 2,6-diphosphofrucoto-2-phosphatase. More speculatively, if the analog does mimic the stimulatory effect of 2,6-diphosphofructose and is stable and inert to FBPase 2, then it may be of use in the treatment of disorders involving glucose metabolism. Carbocyclic analogs of ribosides, including 5-phosphoribosyl-1-pyrophosphate and 5-phosphoribosylamine will be prepared. These molecules are substrates for enzymes active in the synthesis of purine nucleotides and these analogs may be of use as antivial agents. This project will develop a new process for the synthesis of carbocyclic analogs of carbohydrates. The process can be applied in any are where analogs of carbohydrates or glycosides are desired. For example, carbocyclic analogs of glycoside containing antibiotics can be prepared based on this new technology and will be inert to glycosidase enzymes. Finally, a bis-carba analog of AMP will be prepared. This molecule is of interest because it may be able to replace natural AMP in enzymic processes but will be much more robust than the natural molecule. A very stable analog of AMP could find wide application in industrial processes which require ATP for use with immobilized or modified enzymes.

该项目的主要目标是合成碳环类似物 重要的代谢调节剂2,6-二磷酸果糖。 这个分子 是已知最强的酶正效应子 6-磷酸果糖激酶，催化分解的关键控制步骤 葡萄糖或胰高血糖素以提供 ATP。 假设碳环类似物比碳环类似物稳定得多 母体调节剂，很可能对通常情况下的酶呈惰性 水解 2,6-二磷酸果糖、2,6-二磷酸果糖-2-磷酸酶 (FBPase 2）。 该模拟的可用性将允许进行一些有趣的实验 进行这些实验将导致增加 了解磷酸果糖激酶催化的反应 2,6-二磷酸果糖-2-磷酸酶。 更具推测性的是，如果模拟确实 模拟 2,6-二磷酸果糖的刺激作用，并且稳定且 对 FBPase 2 呈惰性，因此可用于治疗疾病 涉及葡萄糖代谢。 核苷的碳环类似物，包括 5-磷酸核糖基-1-焦磷酸和5-磷酸核糖胺将是 准备好了。 这些分子是酶活性的底物 嘌呤核苷酸和这些类似物的合成可用作抗病毒药物 代理。 该项目将开发一种合成碳环化合物的新工艺 碳水化合物的类似物。 该过程可以应用于任何地方 需要碳水化合物或糖苷的类似物。 例如， 可以制备含有抗生素的糖苷的碳环类似物 基于这项新技术，将对糖苷酶呈惰性。 最后，将制备AMP的双卡巴类似物。 这个分子是 人们感兴趣，因为它可能能够在酶促过程中替代天然 AMP 但比天然分子更坚固。 一个非常稳定的 AMP 的类似物可以在工业过程中得到广泛的应用 需要 ATP 与固定化或修饰酶一起使用。