Bridging the Glycome and Proteome with Chemical Biology

用化学生物学连接糖组和蛋白质组

基本信息

批准号：
10609533
负责人：
Mia L Huang
金额：
$ 45.25万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-04-30
项目状态：
未结题

项目摘要

PROJECT SUMMARY Glycoproteins and proteoglycans are important protein glycoconjugates in the cell. They can control many biological events, such as growth factor signaling, cell adhesion, and differentiation, to impact cancer biology, development, and immunity. While vital to human health and physiology, we currently do not have a comprehensive molecular understanding of how these molecules orchestrate their functions. Many techniques study these molecules in isolation – focusing on only the protein or glycan component alone. This current approach severely underappreciates the structural diversity of protein glycoconjugates, and it has left us with a narrowed understanding of how protein glycoforms can differentially regulate biology. Furthermore, it has impeded pathways to use glycoform-dependent interactions for drug discovery. Our research program integrates techniques in chemical biology, molecular biology, and protein engineering, in order to address these gaps. In this application, we describe our plans to create defined semi-synthetic glycoproteins and proteoglycans, and to use these materials to study their interactions in live cells. Identifying the glycoproteins associated with glycan-binding proteins allows the use of targeted genetic approaches to study their functional contributions. The insights developed from these studies will create an opportunity to discover small molecules that can selectively modulate glycan-binding protein and glycoprotein interactions in order to regulate important biological events.

项目概要糖蛋白和蛋白聚糖是细胞中重要的蛋白质糖缀合物。控制许多生物事件，例如生长因子信号传导、细胞粘附和分化，影响癌症生物学、发育和免疫，同时对人类健康和生理至关重要。我们目前还没有对这些分子如何进行全面的分子理解许多技术单独研究这些分子——只关注它们。目前的方法严重低估了蛋白质或聚糖成分。蛋白质糖复合物的结构多样性，这使我们对蛋白质糖型如何差异化地调节生物学此外，它还阻碍了通路。使用糖型依赖性相互作用进行药物发现。化学生物学、分子生物学和蛋白质工程技术，以解决在本申请中，我们描述了创建特定半合成材料的计划。糖蛋白和蛋白聚糖，并使用这些材料来研究它们在活细胞中的相互作用。鉴定与聚糖结合蛋白相关的糖蛋白允许使用靶向遗传方法来研究它们的功能贡献。研究将为发现可以选择性调节的小分子创造机会聚糖结合蛋白和糖蛋白相互作用以调节重要的生物事件。