Chemical Tools for the Investigation and Manipulation of Protein Glycosylation

用于研究和操作蛋白质糖基化的化学工具

基本信息

批准号：
9422572
负责人：
Matthew Robert Pratt
金额：
$ 32.79万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9422572
关键词：
Affect Affinity Alkynes Azides Biological Biology California Carbohydrates Cells Chemicals Chemistry Communities Development Disease Effectiveness Event Fucose Future Global Change Glycoproteins Goals Health Human Imagery Individual Investigation Link Mammalian Cell Maps Mediating Metabolic Methods Modification Molecular Structure Monitor Monosaccharides Nature Phosphotransferases Polysaccharides Post-Translational Protein Processing Process Protein Glycosylation Protein Inhibition Proteins Reaction Reporter Research Role Sialic Acids Signal Transduction Structure Surface Techniques Technology Universities analog analytical tool base crosslink design falls functional group glycosylation glycosyltransferase inhibitor/antagonist innovation new technology novel strategies prevent small molecule inhibitor small molecule libraries sugar tool

项目摘要

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.

摘要 - “用于研究和操纵蛋白质糖基化的化学工具” 该提案的广泛目标是开发化学工具，这些工具将使您能够轻松而健壮糖蛋白的鉴定，特定类型的糖基化的不可自然性以及发现糖基化的发现介导的生物相互作用。翻译后修饰的常见形式，并与各种过程缔结不幸的是，稳定性，大分子相互作用和细胞信号传导。询问功能不足，这将糖基化的研究限制为我们计划的一些专家实验室在三个特定目标中解决这种未满足的需求。记者，重点是为不同类别的糖基化选择化学工具选择性。提议将选择性化学记者直接转化为特定的选择性小分子抑制剂糖基转移率3。特定的照片 - 交联链链接到活细胞，重点是识别生物学相互作用由聚糖介导。