STICS: Surface-Tethered Iterative Carbohydrate Synthesis

STICS：表面束缚的迭代碳水化合物合成

• 批准号: 7096760
• 负责人: Keith J. Stine
• 金额: $ 21.35万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7096760
• 关键词: chemical binding; chemical structure; chemical synthesis; combinatorial chemistry; electrochemistry; electron microscopy; glycosides; glycosylation; gold; oligosaccharides; surface property; technology /technique development; thiols; ultraviolet spectrometry

DESCRIPTION (provided by applicant): Project Summary: The development of STICS (Surface Tethered Iterative Carbohydrate Synthesis), a new approach to the supported synthesis of oligosaccharides, will be pursued. The approach is based on the use of porous gold, chosen for its extremely high surface area and chemical stability. The porous gold films will be created on titanium foil, and then characterized using electron microscopy and electrochemistry. The gold surfaces will then be modified with self-assembled monolayers of tri-thiolated derivatives designed to be stable in organic solvents and provide an initial layer of amine groups for initiation of the step-wise synthetic process. The monolayer surface coverage will be characterized using electrochemistry and solution-depletion measurements using UV-visible spectroscopy. Upon proving the feasibility of the surface modification, our attention will be turned to the development of a new glycosylation methodology on the surface. Novel glycosyl donors, S-benzoxazolyl (SBox) glycosides, will be used for both the attachment of the first monosaccharide and the oligosaccharide chain elongation. At the end of the sequence, the assembled glycostructures on the solid support will be deprotected and made usable for subsequent biological testing. The supports will be stacked in a manner suitable for the creation of small combinatorial libraries of compounds. It is envisioned that these very high surface area supports will be usable in molecular recognition studies using solution depletion measurements and standard assays of protein concentration. The potential application of these supports in ELISA methods will be explored. Relevance: Recognition of the significance of carbohydrate structures in human biology has been growing rapidly in recent years, especially in areas such as immunity and cancer. Lipids and proteins are often found with unique carbohydrate structures attached to them that are crucial for their function. In order to study the ultimate medical significance of these carbohydrates, new approaches are needed to synthesize them and study their behavior.

描述（由申请人提供）：项目摘要：STICS（表面栓系迭代碳水化合物合成）的开发，一种新的支持合成低聚糖的方法，将继续进行。该方法基于多孔金的使用，选择其极高的表面积和化学稳定性。多孔金膜将在钛箔上形成，然后使用电子显微镜和电化学进行表征。然后，金表面将用三硫醇化衍生物的自组装单层进行改性，所述自组装单层被设计为在有机溶剂中稳定，并提供胺基的初始层以用于逐步合成过程的起始。单层表面覆盖率将使用电化学和溶液耗尽测量（使用紫外可见光谱）进行表征。在证明了表面修饰的可行性后，我们的注意力将转向开发一种新的表面糖基化方法。新的糖基供体，S-苯并恶唑基（SBox）糖苷，将用于第一个单糖的连接和寡糖链的延长。在序列结束时，固体支持物上组装的糖结构将被脱保护并可用于随后的生物学测试。支持物将以适合于产生化合物的小组合文库的方式堆叠。据设想，这些非常高的表面积的支持物将可用于分子识别研究，使用溶液消耗测量和蛋白质浓度的标准测定。这些支持物在ELISA方法中的潜在应用将被探索。相关性：近年来，人们对碳水化合物结构在人类生物学中的重要性的认识迅速增长，特别是在免疫和癌症等领域。脂质和蛋白质通常具有独特的碳水化合物结构，这些结构对其功能至关重要。为了研究这些碳水化合物的最终医学意义，需要新的方法来合成它们并研究它们的行为。