STICS: Surface-Tethered Iterative Carbohydrate Synthesis

项目概述：本项目将研究支持合成低聚糖的新方法——表面系缚迭代碳水化合物合成（STICS）。该方法基于多孔金的使用，选择多孔金是因为其极高的表面积和化学稳定性。多孔金薄膜将在钛箔上形成，然后用电子显微镜和电化学方法对其进行表征。然后用自组装的三硫代衍生物单层修饰金表面，这些衍生物被设计成在有机溶剂中稳定，并为启动逐步合成过程提供胺基的初始层。单层表面覆盖将使用电化学和使用紫外可见光谱的溶液损耗测量来表征。在证明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（SBox）糖苷将用于第一个单糖的附着和低聚糖链的延伸。在序列的最后，在固体载体上组装的糖结构将被解除保护，并用于随后的生物测试。支撑将以一种适合创建小型化合物组合库的方式堆叠。设想这些非常高的表面积支持将用于分子识别研究，使用溶液耗尽测量和蛋白质浓度的标准分析。本文将探讨这些载体在酶联免疫吸附法中的潜在应用。相关性：近年来，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。脂质和蛋白质通常带有独特的碳水化合物结构，这对它们的功能至关重要。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。

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.