PENTENYL GLYCOSIDES--TRANSFORMATIONS AT ANOMERIC CENTER

戊烯基糖苷——异头中心的转化

• 批准号: 2770957
• 负责人: Bertram Oliver Fraser-Reid
• 金额: $ 16.65万
• 依托单位: NATURAL PRODUCTS/GLYCOTECHNOLOGY RES INS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2770957
• 关键词: acyl group; alkenes; anomer; chemical cleavage; chemical synthesis; endotoxins; glycoproteins; glycosides; leishmaniasis; lipopolysaccharides; oligosaccharides; pentosan; polyenes; stereochemistry

DESCRIPTION: The principal investigator states that the importance of the project stems from the fact that of the three major families of biopolymers, proteins, oligonucleotides and oligosaccharides, the last is the least well understood because their isolation, structure-proof, and (above all) their laboratory syntheses have been far more difficult and demanding than in the case of the other two. He notes that however, great strides have been made in the techniques of isolation and structure-proof which has made many of these oligosaccharides available intact, and it is now clear that their structures are usually of daunting complexity. He further indicates that with the other two biopolymers, proteins and oligonucleotides, clarification of their biological regulatory roles accelerated markedly with the advent of synthetic methods that made them and/or their analogs, readily available for structure activity correlations. It is noted that oligosaccharides usually being the primary recognition agents on cell surfaces is now widely appreciated, this step being a prelude to subsequent critical events such as enzymolysis, cell penetration, etc and that thus bacteria, viruses, (many) hormones, other cells, etc. must engage in this first step, and hence undesirable events (such as bacterial infection) can conceivably be prevented by the use of mimics to negate the recognition step. It is further noted that on the other hand, beneficial interactions, as in the case of hormones, can be facilitated so as to enhance recognition. The principal investigator states that these visionary health-related benefits rely ultimately on ready access to synthetic oligosaccharides, or fragments and modifications thereof for biochemical evaluation and structure-activity investigations. He notes that since their discovery in his laboratory six years ago, n-pentenyl glycosides have proved to be versatile synthetic precursors for several oligosaccharides and glycoproteins and that with their credibility thereby established, he envisages greatly extending their synthetic potential to address problems associated with major health hazards. It is stated that examples of these include the lipopolysaccharides associated with Leishmaniasis and the endotoxin from lipid A and that exploratory studies aimed at developing methodology for these targets is an important segment of the proposal.

描述：主要研究者指出， 该项目源于这样一个事实，即在生物聚合物的三大家族中， 蛋白质，寡核苷酸和寡糖，最后一种是最不好的 之所以被理解，是因为它们的隔离性、抗结构性以及（最重要的是）它们的 实验室合成比以前更加困难和要求更高 其他两个的情况。 他指出，然而， 在隔离和防结构技术方面， 这些寡糖可以完整地获得，现在很清楚，它们的 结构通常是令人生畏的复杂性。 他进一步指出， 与其他两种生物聚合物，蛋白质和寡核苷酸，澄清 它们的生物调节作用随着 制备它们和/或它们的类似物的合成方法， 结构活性相关性 应注意，寡糖通常 作为细胞表面的主要识别剂， 这一步骤是随后关键事件的前奏， 细菌，病毒，（许多） 激素，其他细胞等必须参与这第一步，因此， 可以想象，不良事件（例如细菌感染）可能会 通过使用模仿来否定识别步骤来防止。 是 还指出，另一方面， 激素的情况下，可以促进，以提高识别。 首席研究员指出，这些有远见的健康相关的 这些益处最终取决于合成低聚糖的易得性，或 用于生物化学评价的片段及其修饰， 结构活性研究。 他指出，自从他们在1999年被发现以来， 六年前，他的实验室已经证明， 多种寡糖的通用合成前体， 糖蛋白和他们的信誉，从而建立，他 设想大大扩展其合成潜力，以解决问题 与重大健康危害有关。 据指出，这些例子 包括与利什曼病相关的脂多糖， 脂质A中的内毒素以及旨在开发 实现这些目标的方法是建议的一个重要部分。