Glycoscience Tools and Therapeutics

糖科学工具和疗法

• 批准号: 10715888
• 负责人: Mark Patrick Farrell
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715888
• 关键词: Address; Affinity; Binding; Biochemical; Biological Assay; Biology; Carbohydrates; Cell Proliferation; Cells; Communities; Covalent Interaction; Development; Disease; Embryonic Development; Enzyme-Linked Immunosorbent Assay; Fertilization; Functional disorder; Glycobiology; Hormonal; Human; Label; Ligands; Mediating; Pathogenesis; Pathway interactions; Physiology; Play; Polysaccharides; Process; Protein-Carbohydrate Interaction; Proteins; Role; Sorting; Techniques; Technology; Therapeutic; Viral; biological systems; biophysical techniques; carbohydrate binding protein; carbohydrate receptor; neuron development; tool

SUMMARY Carbohydrate-protein interactions mediate important processes in human physiology and pathophysiology, but the study of these important interactions remains challenging and highly specialized. A major contributor to this problem is the weak binding affinity of many carbohydrate-protein interactions, which limits the applicability of many commonly applied biochemical and biophysical techniques (e.g., ELISA, ITC). This can be somewhat rectified if natural or synthetic multivalent ligands can be utilized, but in many cases, molecules of this sort are challenging to synthesize and/or isolate. The development of glycan microarrays has pushed the glycobiology field forward by enabling numerous groundbreaking studies; however, this technology has yet to become widely available and can only be utilized when a carbohydrate binding protein has been identified by other means. As such there is currently a gap between discovery and downstream assays that needs to be filled to push the field forward. In this proposal we are addressing this gap by developing tools that can identify carbohydrate-protein interactions, using techniques that are widely available to the scientific community. The tools that we are developing circumvent the challenge presented by the low affinity carbohydrate-protein interactions by covalently labeling the carbohydrate binding protein in a carbohydrate directed manner. Here, we propose to: (i) advance the utility of this approach; and (ii) apply this approach to ask important questions in biology and to target disease relevant pathways.

摘要 碳水化合物-蛋白质相互作用在人体生理学和病理生理学中起着重要的作用，但是 对这些重要相互作用的研究仍然具有挑战性和高度专业性。这其中的一个主要贡献者 问题是许多碳水化合物-蛋白质相互作用的结合亲和力很弱，这限制了 许多常用的生化和生物物理技术(例如，酶联免疫吸附试验、国际贸易中心)。这可能会有一些 如果可以利用天然或合成的多价配体，则可以进行精馏，但在许多情况下，这类分子是 具有合成和/或分离的挑战性。糖链微阵列的发展推动了糖生物学的发展 通过实现大量开创性的研究来推动领域的发展；然而，这项技术还没有广泛应用 只有在通过其他手段鉴定了碳水化合物结合蛋白后才能使用。AS 目前，在发现和下游化验之间存在差距，需要填补这一差距才能推动这一领域的发展 往前走。在这项提案中，我们正在通过开发能够识别碳水化合物-蛋白质的工具来解决这一差距 互动，使用科学界广泛可用的技术。我们所拥有的工具 发展中通过共价来规避低亲和力碳水化合物-蛋白质相互作用带来的挑战 以碳水化合物定向的方式标记碳水化合物结合蛋白。在此，我们建议：(一)推进 这种方法的实用性；和(Ii)应用这种方法来提出重要的生物学问题和针对疾病 相关路径。