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资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。项目IV：Kiick人工糖蛋白用于材料科学和生物学中的特定多价相互作用，蛋白质与糖水之间的多价相互作用控制了与病毒感染，肿瘤转移和炎症反应有关的识别过程。众所周知，糖的身份，显示在其上的模板的性质以及模板上糖的数量是结合中的重要变量。但是，有目的的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中都是异质的。因此，控制分子量，成分和糖水放置的糖聚合物支架的产生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，我们正在采用蛋白质工程方法来生产良好控制的聚合物结构，在这些聚合物结构中，可以实现糖糖沿聚合物链的精确放置。我们已经合成了大约10个螺旋和随机线圈蛋白聚合物的初始组，该聚合物在指定和多样的位置含有化学反应性谷氨酸基团。我们还用糖水有效地衍生了这些蛋白质。策略涉及胺糖和谷氨酸之间的酰胺键形成。我们已经进行了初始的免疫化学测定法，以不同的结构与毒素靶标的糖磷酸多肽结合，初步结果表明结合对建筑变量的依赖性。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。