Bridging the Glycome and Proteome with Chemical Biology

用化学生物学连接糖组和蛋白质组

• 批准号: 10415215
• 负责人: Mia L Huang
• 金额: $ 44.37万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10415215
• 关键词: Address; Behavior; Binding Proteins; Biological; Biology; Cancer Biology; Cell Adhesion; Cells; Chemicals; Development; Event; Glycoconjugates; Glycoproteins; Growth Factor; Health; Health Promotion; Human; Immunity; Intervention; Left; Molecular; Molecular Biology; Nature; Pathway interactions; Physiology; Polysaccharides; Protein Analysis; Protein Engineering; Proteins; Proteoglycan; Proteome; Research; Signal Transduction; Structure; Techniques; drug discovery; genetic approach; insight; programs; small molecule

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.

项目摘要 糖蛋白和蛋白聚糖是细胞中重要的蛋白质糖缀合物。他们可以 控制许多生物事件，例如生长因子信号传导，细胞粘合剂和分化， 影响癌症生物学，发育和免疫学。尽管对人类健康和生理学至关重要，但 目前，我们对这些分子的方式尚无全面的分子理解 策划他们的功能。许多技术分别研究了这些分子 - 仅关注 单独使用蛋白质或聚糖成分。这种当前的方法严重低估了 蛋白质糖缀合物的结构多样性，这使我们对 蛋白质糖剂如何不同地调节生物学。此外，它阻碍了途径 使用糖剂依赖性相互作用进行药物发现。我们的研究计划集成了 化学生物学，分子生物学和蛋白质工程技术，以解决 这些差距。在此应用程序中，我们描述了创建定义的半合成计划的计划 糖蛋白和蛋白聚糖，并使用这些材料研究其在活细胞中的相互作用。 识别与聚糖结合蛋白相关的糖蛋白可以使用靶向 研究其功能贡献的遗传方法。这些见解是从这些开始的 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，以调节重要的生物学 事件。