Glycoproteins via Chemoselective Ligation of Proteins and Glycans

化学部的化学合成项目支持Philip Garner教授的这个项目。加纳教授是华盛顿州立大学化学系的一名教员。他正在开发糖蛋白合成的新方法，糖蛋白广泛存在于真核细胞中，在细胞-细胞信号传导、免疫反应和神经元发育中起着重要作用。糖蛋白的研究因其难以获得而受到限制。该项目混合了化学和生物学方法，开发了一套新的工具，用于将聚糖结合到无保护的肽和最终的蛋白质上。由于其跨学科的性质，它非常适合各级科学家的教育。加纳教授的团队也处于有利地位，可以为在科学领域代表性不足的学生提供最高水平的教育和培训。涉及当地社区大学生的外展活动也是资助项目的一部分。该项目开发了糖蛋白的聚合合成方法，特别关注可用于组装糖磷脂酰肌醇（GPI）共轭蛋白和n -糖蛋白的反应。这两种翻译后蛋白修饰广泛存在于真核细胞中，并在多种生物过程中发挥重要作用。糖基化蛋白的研究由于难以以均匀的形式获得这些物质而受到限制。目前可用的化学酶方法要么不能产生天然结构（gpi偶联蛋白），要么不是一般的（n -糖蛋白）。该项目正在开发一种基于Cu（II）介导的蛋白质硫酸和聚糖胺偶联的解决方案。这些Cu（II）介导的偶联反应与其他连接反应的区别在于它们具有更高的速率和化学选择性，这似乎是一种独特的反应机制的功能。这种方法新颖，理论上可以应用于任何GPI-和n -糖蛋白。gpi蛋白在神经元、成纤维细胞、内皮细胞和许多其他细胞表面表达。该项目培养研究生和本科生有机合成及其在生物分子中的应用。这项活动有利于我们的社会，为新一代学生在学术界或制药/生物技术部门的职业生涯做好准备。该项目通过计划中的研讨会解决了当地社区学院的学生和教师与积极从事大学研究的科学家之间目前有限的互动。

The Chemical Synthesis Program of the Chemistry Division supports this project by Professor Philip Garner. Professor Garner is a faculty member in the Department of Chemistry at Washington State University. He is developing new methodology for the synthesis of glycoproteins, which are found widely in eukaryotic cells and play important roles cell-cell signaling, immune response, and neuronal development. The study of glycoproteins has been limited by their inaccessibility. This project blends chemical and biological approaches to develop a new suite of tools for the conjugation of glycans to both unprotected peptides and ultimately proteins. Because of its interdisciplinary nature, it is well suited for the education of scientists at all levels. Professor Garner's group is also well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving local community college students are also part of the funded project.   The project develops methodology for the convergent synthesis of glycoproteins, specifically focusing on reactions that could be used for the assembly of glycophosphatidylinositol (GPI)-conjugated proteins and N-glycoproteins. Both of these posttranslational protein modifications are found widely in eukaryotic cells and play important roles in a variety of biological processes. The study of glycosylated proteins has been limited by the difficulty in obtaining these substances in homogeneous form. Currently available chemoenzymatic approaches either do not produce native structures (GPI-conjugated proteins) or are not general (N-glycoproteins). This project is developing a solution that is based on the Cu(II)-mediated coupling of protein thioacids and glycan amines. These Cu(II)-mediated couplings are distinguished from other ligation reactions by their enhanced rates and chemoselectivities, which appear to be a function of a unique reaction mechanism. The approach is novel and could, in theory, be applied to any GPI- and N-glycoprotein. GPI-proteins are expressed on the surface of neurons, fibroblasts, endothelial cells and many other cell types. The project trains both graduate and undergraduate students in organic synthesis and its application to biological molecules. This activity benefits our society by preparing a new generation of students for careers in either academia or the pharmaceutical/biotech sectors. The project addresses the currently limited interaction of students and faculty at local community colleges with scientists actively engaged in research at the university level through a planned symposium.