SYNTHETIC ANALOGS OF FRUCTOSE PHOSPHATES AND RIBOSIDES

本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。 这种分子 是该酶已知的最强的正效应子 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来提供ATP。 假设碳环类似物比碳环类似物稳定得多。 亲本调节剂，并且可能对通常 水解2，6-二磷酸果糖，2，6-二磷酸果糖-2-磷酸酶（FBPase 2）。 这种类似物的可用性将允许几个有趣的实验 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。 更大胆地推测，如果模拟物 模拟2，6-二磷酸果糖的刺激作用，并且稳定， 对FBPase 2呈惰性，则其可用于治疗病症 包括葡萄糖代谢。 核苷的碳环类似物，包括 5-磷酸核糖基-1-焦磷酸和5-磷酸核糖胺将被 制备 这些分子是酶的底物，这些酶在细胞中具有活性。 合成嘌呤核苷酸和这些类似物可用作抗病毒药物 剂. 本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。 比如说， 可以制备含有抗生素的糖苷的碳环类似物 基于这种新技术，并且对糖苷酶是惰性的。 最后，将制备AMP的bis-carba类似物。 这个分子是 因为它可能能够在酶促过程中替代天然AMP 但会比天然分子更坚固。 一个非常稳定 AMP的类似物可以在工业过程中得到广泛的应用， 需要ATP用于固定化或修饰的酶。

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.