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: 7960412
• 负责人: Kristi L Kiick
• 金额: $ 31.34万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960412
• 关键词: Affinity; Amides; Architecture; Binding; Biocompatible Materials; Biological Assay; Biology; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Dependence; Funding; Glutamic Acid; Glycoproteins; Grant; Inflammatory Response; Institution; Methods; Molecular Biology; Molecular Weight; Nature; Neoplasm Metastasis; Polymers; Positioning Attribute; Process; Production; Property; Protein Engineering; Proteins; Research; Research Personnel; Resources; Science; Source; Specific qualifier value; Targeted Toxins; Tumor Virus Infections; United States National Institutes of Health; cellular targeting; design; polypeptide; random coil (protein); scaffold

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.

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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RNA之间的特异性多价相互作用控制涉及病毒感染、肿瘤转移和炎症反应的识别过程。 已知糖的身份、其所展示的模板的性质以及模板上的碱基数目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一直是非常困难的，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、组成和糖的位置受到控制的糖聚合物支架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，我们采用蛋白质工程的方法，生产良好控制的聚合物结构，其中的精确放置，沿沿着一个聚合物链可以实现。 我们已经合成了一个初始的一组约10螺旋和随机卷曲蛋白聚合物，含有化学反应性谷氨酸基团在指定的和不同的位置。我们还有效地衍生这些蛋白质与氨基化的氨基化的谷氨酸和谷氨酸之间的酰胺键的形成策略。我们已经进行了初步的免疫化学试验的糖基化多肽的结合不同的架构毒素的目标，初步结果表明依赖于建筑变量的结合。 这些独特分子的构象特性和结合亲和力的其他表征正在进行中。