UDE COBRE: ARTIFICIAL GLYCOPROTEINS FOR APPLICATIONS IN MATERIALS AND BIOLOGY

UDE COBRE：用于材料和生物学应用的人造糖蛋白

• 批准号: 7381975
• 负责人: Kristi L Kiick
• 金额: $ 25.06万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381975
• 关键词: UDE; COBRE; ARTIFICIAL; GLYCOPROTEINS; APPLICATIONS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project IV: Kiick Artificial Glycoproteins for Application in Materials Science and Biology Specific multivalent interactions between proteins and saccharides control the recognition processes involved in virus infection, tumor metastasis, and inflammatory responses. It is known that the identity of the saccharide, the nature of the template on which it is displayed, and the number of saccharides on the template are important variables in binding. However, purposeful design of polymeric materials to manipulate these interactions has been very difficult, since all chemically synthesized polymeric materials are heterogeneous in both molecular weight and composition. The production of glycopolymer scaffolds in which molecular weight, composition, and saccharide placement are controlled would therefore offer enormous advantages for designing materials capable of interacting with specific protein or cellular targets. In this project, we are employing protein engineering methods for the production of well-controlled polymeric architectures in which the precise placement of saccharides along a polymer chain can be realized. We have synthesized an initial set of approximately 10 helical and random coil protein polymers that contain chemically reactive glutamic acid groups at specified and varied positions. We have also efficiently derivatized these proteins with saccharides; strategies have involved amide bond formation between aminated saccharides and glutamic acid. We have conducted initial immunochemical assays of the binding of glycoslylated polypeptides of varying architectures to toxin targets, and preliminary results suggest a dependence of binding on architectural variables. Additional characterization of the conformational properties and binding affinities of these unique molecules is underway.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。项目四：Kiick 人工糖蛋白在材料科学和生物学中的应用蛋白质和糖之间的特定多价相互作用控制着病毒感染、肿瘤转移和炎症反应中涉及的识别过程。已知糖的身份、其所展示的模板的性质以及模板上糖的数量是结合中的重要变量。然而，有目的地设计聚合物材料来操纵这些相互作用非常困难，因为所有化学合成的聚合物材料在分子量和组成上都是异质的。因此，控制分子量、组成和糖分布的糖聚合物支架的生产将为设计能够与特定蛋白质或细胞靶标相互作用的材料提供巨大的优势。在这个项目中，我们采用蛋白质工程方法来生产控制良好的聚合物结构，其中可以实现糖沿着聚合物链的精确放置。我们合成了一组初始的大约 10 种螺旋和无规卷曲蛋白质聚合物，它们在特定和不同的位置含有化学反应性谷氨酸基团。我们还用糖类有效地衍生了这些蛋白质；策略涉及胺化糖和谷氨酸之间的酰胺键形成。我们对不同结构的糖基化多肽与毒素靶标的结合进行了初步的免疫化学测定，初步结果表明结合对结构变量的依赖性。这些独特分子的构象特性和结合亲和力的进一步表征正在进行中。