Chemical Tools for the Investigation and Manipulation of Protein Glycosylation

摘要-“研究和操纵蛋白质糖基化的化学工具” 该提案的总体目标是开发化学工具，使人们能够轻松、稳健地 糖蛋白的鉴定，特定类型糖基化的抑制，以及糖基化的发现- 介导的生物相互作用。将碳水化合物添加到蛋白质中，或糖基化，是最重要的方法之一。 翻译后修饰的常见形式，并与各种过程，包括蛋白质 稳定性、大分子相互作用和细胞信号传导。不幸的是，目前可用的工具 对这些功能的研究还不够，这就限制了对糖基化的研究，使之仅限于少数专业实验室。我们计划 在三个具体目标中解决这一未满足的需求。目标1建立在我们的代谢化学的发展 报道，重点是使这些化学工具对不同类别的糖基化具有选择性。目的2 提出直接将选择性化学报告物转化为特异性的选择性小分子抑制剂， 糖基转移酶目的3利用糖基化的化学酶修饰的优点， 特定的光交联剂到活细胞上，重点是确定生物相互作用， 由聚糖介导。

ABSTRACT - “Chemical Tools for the Investigation and Manipulation of Protein Glycosylation” The broad goal of this proposal is the development of chemical tools that will enable the facile and robust identification of glycoproteins, inhibition of specific types of glycosylation, and the discovery of glycosylation- mediated biological interactions. The addition of carbohydrates to proteins, or glycosylation, is one of the most common forms of posttranslational modifications and is associated with various processes, including protein stability, macromolecular interactions, and cellular signaling. Unfortunately, the currently available tools for interrogating these functions fall short, which limits the study of glycosylation to a few expert labs. We plan to tackle this unmet need in three specific aims. Aim 1 builds on our development of metabolic chemical reporters, with a focus on making these chemical tools selective for different classes of glycosylation. Aim 2 proposes to directly transform selective chemical reporters into selective small-molecule inhibitors of specific glycosyltransferases. Aim 3 leverages the advantages of chemoenzymatic modification of glycosylation to install specific photo-cross-linkers onto living cells, with a focus on identifying biological interactions that are mediated by glycans.