UDE COBRE: ARTIFICIAL GLYCOPROTEINS FOR APPLICATIONS IN MATERIALS AND BIOLOGY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。项目IV：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特定的多价相互作用控制着病毒感染、肿瘤转移和炎症反应所涉及的识别过程。已知，糖的特性、其上显示糖的模板的性质以及模板上的糖的数量是结合的重要变量。然而，有目的地设计聚合物材料来操纵这些相互作用一直是非常困难的，因为所有化学合成的聚合物材料在相对分子质量和组成上都是不均匀的。因此，控制分子量、组成和糖的放置的糖共聚物支架的生产将为设计能够与特定蛋白质或细胞靶点相互作用的材料提供巨大的优势。在这个项目中，我们正在使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。我们已经合成了一组大约10个螺旋和随机卷曲的蛋白质聚合物，它们在特定和不同的位置含有化学活性谷氨酸基团。我们还用糖有效地衍生了这些蛋白质；策略包括在氨基糖和谷氨酸之间形成酰胺键。我们已经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分析，初步结果表明结合依赖于结构变量。对这些独特分子的构象性质和结合亲和力的进一步表征正在进行中。

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.