Fluorous Solution-Phase Synthesis of Peptides

描述（由申请人提供）：随时获得各种低聚糖和糖肽对于糖生物学和糖组学的发展至关重要-低聚糖与其他生物分子（如蛋白质）相互作用的全系统研究。该项目的长期目标是开发一种新的制备规模合成方法，利用Fluorous Technologies的专有标记和纯化技术，合成纯度极高的寡肽、低聚糖和糖肽。该STTR提案第一阶段的具体目标是：1)发展氟-芴基甲氧羰基（F-Fmoc）溶液相寡肽合成（F-Fmoc战略）；2)氟标记辅助低聚糖合成的研究进展；3)氟标记辅助寡糖微阵列和多孔板阵列的发展。这些发展将为该项目的第二阶段奠定基础，其中包括(1)平行合成低聚糖和糖肽文库，这些文库已被报道显示出有趣的生物活性，如对癌细胞的免疫原性；(2)使用平行合合器、液体处理机和自动荧光闪光色谱系统开发自动化溶液相低聚物合成。(3)进一步探索用于直接复合阵列生产的含氟标签。

DESCRIPTION (provided by applicant): Ready access to various oligosaccharides and glycopeptides is crucial for the development of glycobiology and glycomics-the system-wide study of the interactions of oligosaccharides with other biomolecules such as proteins. The long-term goal of the proposed project is to develop a new method for preparative scale syntheses of exceptionally pure oligopeptides, oligosaccharides, and glycopeptides utilizing Fluorous Technologies' proprietary tagging and purification techniques. The specific aims during Phase I of this STTR proposal are: 1) the development of fluorous-fluorenylmethoxycarbonyl (F-Fmoc) solution-phase oligopeptide synthesis (F-Fmoc Strategy); 2) the development of fluorous tag aided oligosaccharide synthesis; and 3) the development of fluorous tag aided oligosaccharide microarrays and multiwell-plate arrays. These developments will lay the foundation for the project's Phase II, which will include (1) parallel synthesis of oligosaccharide and glycopeptide libraries that have been reported to exhibit interesting biological activities such as immunogenicity against cancer cells, (2) development of automated solution-phase oligomer synthesis using a parallel synthesizer, a liquid handler, and an automated fluorous flash chromatography system, and (3) further exploration of fluorous tags for direct compound array production.