Metabolic Engineering with Bioorthogonal Chemical Reporters

这个项目的主要目标是应用我们实验室开发的一项名为代谢的技术 低聚糖工程以体内成像的全球变化与糖类相关 胚胎发育和癌症。“糖链”是细胞在生长过程中产生的糖链的总和。 特定的时间、空间和环境条件。糖糖组成和分布的变化 与胚胎发生和癌症进展有关。我们寻求开发用于成像的化学工具 生物体中动态的细胞表面糖类。 我们计划追求五个具体目标，进一步扩大葡聚糖成像技术的范围和 将我们的方法应用于生物调查的新途径。目标1直接从我们正在进行的工作中构建 在斑马鱼成像中，随着焦点转移到这种有机体的疾病模型上。Aim 2寻求扩大 利用葡聚糖成像技术对细菌系统进行成像，用眼睛监测外膜的变化 可能与发病机制相关的糖脂和荚膜多糖。目标3侧重于， 在我们早期工作的基础上，开发用于在小鼠肿瘤模型中成像多聚糖的探针 模型生物。Aim 4寻求用第二代生物正交化反应提纲 四环烷连接化学以及基于亚膦硼烷的新反应。

The broad objective of this project is to apply a technique developed in our lab termed metabolic oligosaccharide engineering to in vivo imaging of global changes in the glycome associated with embryonic development and cancer. The "glycome" is the totality of glycans that cells produce under specified conditions of time, space and environment. Changes in the glycome's composition and distribution are associated with embryogenesis and cancer progression. We seek to develop chemical tools for imaging the dynamic cell-surface glycome in living organisms. We plan to pursue five specific aims that further expand the scope of the glycan imaging technology and apply our methods to new avenues of biological investigation. Aim 1 builds directly from our ongoing work in zebrafish imaging, with a shift in focus to disease models in this organism. Aim 2 seeks to expand the glycan imaging technique to bacterial systems, with an eye for monitoring changes in outer membrane glycolipids and capsular polysaccharides that might correlate with pathogenesis. Aim 3 focuses on the , development of probes for imaging glycans in mouse tumor models, building from our earlier work in this model organism. Aim 4 seeks to build the bioorthogonal reaction compendium with second-generation quadricyclane ligation chemistries as well as new reactions based on phosphinoboranes.