UDE COBRE: ARTIFICIAL GLYCOPROTEINS FOR APPLICATIONS IN MATERIALS AND BIOLOGY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。项目四：人造糖蛋白在材料科学和生物学中的应用蛋白质和糖类之间的特异性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。众所周知，糖的身份，它所显示的模板的性质，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是非常困难的，因为所有化学合成的聚合物材料在分子量和组成上都是不均匀的。因此，生产分子量、组成和糖的放置都受到控制的糖共聚物支架，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，我们正在使用蛋白质工程方法来生产控制良好的聚合物结构，其中糖沿着聚合物链的精确位置可以实现。我们已经合成了一组初始的大约10个螺旋状和随机线圈状的蛋白质聚合物，这些聚合物在特定的和不同的位置含有化学活性的谷氨酸基团。我们还用糖有效地衍生了这些蛋白质；策略包括胺化糖和谷氨酸之间形成酰胺键。我们对不同结构的糖基化多肽与毒素靶点的结合进行了初步的免疫化学分析，初步结果表明，这种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.