Automation of Surface-Tethered Iterative Carbohydrate Synthesis (STICS)

表面束缚碳水化合物迭代合成 (STICS) 的自动化

• 批准号: 8766200
• 负责人: ALEXEI V DEMCHENKO
• 金额: $ 26.69万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8766200
• 关键词: Academia; Address; Area; Attention; Autoimmune Diseases; Automation; Bacterial Infections; Biochemistry; Biological; Biological Assay; Biological Sciences; Carbohydrate Chemistry; Carbohydrates; Chemicals; Chemistry; Chromatography; Collaborations; Communities; Complex; Computer Interface; Computer software; Development; Diagnostic; Discipline; Disease; Equipment; Evaluation; Evolution; Future; Generations; Genomics; Globosides; Goals; Gold; Government; Grant; Health; High Pressure Liquid Chromatography; Human; Industry; Knowledge; Laboratories; Left; Life; Malignant Neoplasms; Manuals; Medical; Medicine; Methodology; Methods; Mind; Monitor; National Institute of General Medical Sciences; Nature; Oligosaccharides; Organic Synthesis; Organism; Phase; Polynucleotides; Polysaccharides; Preparation; Procedures; Proteomics; Reaction Time; Reagent; Reporting; Research; Role; S Phase; Science; Scientist; Societies; Solid; Solutions; Solvents; Structure; Surface; Technology; Testing; Therapeutic; Therapeutic Agents; Time; United States National Academy of Sciences; analytical tool; base; carbohydrate structure; cost; detector; experience; glycosylation; improved; innovation; interest; monolayer; nanomaterials; novel; programs; protein aminoacid sequence; research and development; sugar; therapeutic vaccine; time use; tumor; user-friendly

DESCRIPTION (provided by applicant): Automation of Surface-Tethered Iterative Carbohydrate Synthesis (STICS) Project Summary Carbohydrates form the basis of all living organisms and, as a consequence, are ubiquitous both in nature as biologically active compounds and in medicine as therapeutics. Although there has been continued interest in the synthesis of carbohydrates, and the inherent complexity of these molecules consistently captures the attention of many scientists, methods for the isolation, chemical or enzymatic synthesis, analysis, and application of carbohydrates remain cumbersome. Ever-increasing time constraints and cost limitations on research and development in glycoscience and glycotechnology call for the development of rapid, efficient and operationally simple procedures. While this represents an immense task, as acknowledged in the recent National Academy of Sciences report "Transforming glycoscience: a roadmap for the future," this proposal will focus on the introduction of a new, simple automation platform into the synthesis, evaluation, and application of carbohydrates on solid supports. Current automated methods for the synthesis of oligosaccharides are highly sophisticated, operationally complex, and require significant user know-how. On the other hand, high performance liquid chromatography (HPLC) equipment based automation introduced by our laboratories is by far a more attractive method. This is because almost all experimentalists have operational knowledge of and easy access to HPLC equipment. HPLC-assisted synthesis offers not only operational simplicity, but also convenient real-time reaction monitoring of every step using detectors and standard computer software and interface. We already achieved faster reaction times using less reactant, reagent and solvent than manual solid-phase synthesis. However, HPLC-based automation does have the inherent drawbacks of traditional solid-phase synthesis. Building upon promising preliminary results acquired during the development of HPLC-based and STICS approaches, this proposal aims to generate a user-friendly, universal platform for automated and monitored synthesis. This proposal is organized into four Specific Aims dedicated to: 1) new concepts for chemical glycosylation; 2) the refining of all aspects of HPLC-assisted synthesis; 3) the preparation and application of nanoporous materials as solid supports; and 4) the development of synthetic and analytical tools for studying tumor- associated markers. Upon completion of the proposed studies, we expect to have acquired a reliable and simple platform for automated oligosaccharide synthesis. Many classes of compounds can be obtained using solid supports; therefore, the proposed study is expected to be of valuable methodological and practical use to all scientists. Practically anyone with access to basic HPLC equipment should be able to perform automated synthesis and real-time reaction monitoring. Synthesis of carbohydrates and other classes of biomolecules using this user-friendly, automated platform will accelerate discovery in many scientific disciplines and, hence, significantly impact technology, society, the economy and human health.

描述（由申请人提供）：表面束缚迭代碳水化合物合成（Stics）的自动化项目汇总碳水化合物构成了所有生物体的基础，因此，在生物学活性化合物和药物中作为治疗疗法在本质上都是无处不在的。尽管对碳水化合物的合成一直存在感兴趣，而这些分子的固有复杂性始终抓住许多科学家的注意，，分离，化学或酶促合成的方法，碳水化合物的分析，分析和应用仍然很麻烦。在糖科和糖基因研究中对时间限制和成本限制越来越多，要求开发快速，高效和操作简单的程序。尽管这代表了一项艰巨的任务，但正如最近的美国国家科学院报告中所承认的“转化糖科学：未来的路线图”，但该提案将重点介绍将新的，简单的自动化平台引入合成，评估和碳水化合物在固体支持上的应用。当前合成寡糖的自动化方法是高度复杂的，操作上复杂的，并且需要重要的用户专业知识。另一方面，我们实验室引入的基于高性能液相色谱（HPLC）设备的自动化是迄今为止更具吸引力的方法。这是因为几乎所有实验者都有对HPLC设备的操作知识，并且可以轻松访问HPLC设备。 HPLC辅助合成不仅提供操作简单性，还提供了使用检测器以及标准的计算机软件和接口对每个步骤进行方便的实时反应监视。与手动固相合成相比，使用反应物，试剂和溶剂较少的反应时间已经实现了更快的反应时间。但是，基于HPLC的自动化确实具有传统固相合成的固有缺点。在基于HPLC和Stics方法的开发过程中获得的有希望的初步结果的基础，该建议旨在为自动化和受监测的综合生成一个用户友好的通用平台。该提议分为四个专门针对：1）化学糖基化的新概念； 2）HPLC辅助合成的各个方面的完善； 3）纳米多孔材料作为固体支撑的准备和应用； 4）开发用于研究肿瘤相关标记的合成和分析工具。拟议的研究完成后，我们希望获得一个可靠且简单的平台，用于自动寡糖合成。可以使用固体载体获得许多类别的化合物；因此，拟议的研究预计对所有科学家都具有宝贵的方法论和实际用途。实际上，任何可以使用基本HPLC设备的人都应该能够执行自动合成和实时反应监测。使用此用户友好的自动化平台合成碳水化合物和其他类别的生物分子，将加速许多科学学科的发现，从而显着影响技术，社会，经济和人类健康。