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: 9565818
• 负责人: ALEXEI V DEMCHENKO
• 金额: $ 9.73万
• 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 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9565818
• 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; 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; Solvents; Structure; Surface; Technology; Testing; Therapeutic; Therapeutic Agents; Time; United States National Academy of Sciences; Vaccines; analytical tool; base; carbohydrate structure; cost; detector; experience; glycosylation; high standard; improved; innovation; interest; monolayer; nanomaterials; novel; programs; protein aminoacid sequence; public health relevance; research and development; sugar; symposium; 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）的自动化项目摘要碳水化合物形成所有活生物体的基础，因此，在自然界中作为生物活性化合物和在医学中作为治疗剂都是普遍存在的。尽管人们对碳水化合物的合成一直很感兴趣，并且这些分子的固有复杂性一直吸引着许多科学家的注意，但用于碳水化合物的分离、化学或酶促合成、分析和应用的方法仍然很繁琐。糖科学和糖技术研究和开发的时间限制和成本限制不断增加，要求开发快速、高效和操作简单的程序。虽然这是一项艰巨的任务，但正如美国国家科学院最近的报告“转化糖科学：未来的路线图”所承认的那样，该提案将专注于将一种新的简单自动化平台引入固体支持物上碳水化合物的合成，评估和应用。目前用于合成寡糖的自动化方法非常复杂，操作复杂，并且需要大量的用户专业知识。另一方面，我们实验室引进的基于自动化的高效液相色谱（HPLC）设备是一种更有吸引力的方法。这是因为几乎所有的实验人员都有HPLC设备的操作知识和容易获得。高效液相色谱辅助合成不仅操作简单，而且使用检测器和标准计算机软件和界面对每个步骤进行方便的实时反应监测。我们已经实现了更快的反应时间，使用更少的反应物，试剂和溶剂比手动固相合成。然而，基于HPLC的自动化确实具有传统固相合成的固有缺点。该建议以在开发基于高效液相色谱法和科技创新控制系统方法期间取得的有希望的初步结果为基础，旨在为自动化和监测合成创建一个用户友好的通用平台。该提案分为四个具体目标，致力于：1）化学糖基化的新概念; 2）HPLC辅助合成的所有方面的改进; 3）作为固体支持物的纳米多孔材料的制备和应用;以及4）用于研究肿瘤相关标志物的合成和分析工具的开发。在完成拟议的研究后，我们希望获得一个可靠和简单的自动化寡糖合成平台。许多类别的化合物可以得到使用固体支持物，因此，拟议的研究预计将是有价值的方法和实际使用的所有科学家。实际上，任何能够使用基本HPLC设备的人都应该能够进行自动化合成和实时反应监测。使用这种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，从而对技术、社会、经济和人类健康产生重大影响。