Automation of Surface-Tethered Iterative Carbohydrate Synthesis (STICS)

描述(由申请人提供)：表面系留迭代碳水化合物合成的自动化(STICS)项目概述碳水化合物构成了所有生物的基础，因此，在自然界中作为生物活性化合物普遍存在，在医学上也作为治疗药物。虽然人们对碳水化合物的合成一直很感兴趣，而且这些分子固有的复杂性一直吸引着许多科学家的注意，但碳水化合物的分离、化学或酶合成、分析和应用的方法仍然很繁琐。越来越多的时间限制和成本限制在糖科学和糖技术的研究和开发中要求开发快速、高效和操作简单的程序。虽然这是一项艰巨的任务，正如美国国家科学院最近的报告《转变糖科学：未来的路线图》所承认的那样，这项提议将重点放在将一个新的、简单的自动化平台引入固体载体上的碳水化合物的合成、评估和应用。目前用于低聚糖合成的自动化方法非常复杂，操作复杂，需要大量的用户知识。另一方面，我们实验室引进的基于高效液相色谱(HPLC)设备的自动化是一种更具吸引力的方法。这是因为几乎所有的实验者都有操作知识，而且很容易接触到高效液相设备。高效液相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一步进行方便的实时反应监测。我们已经实现了比人工固相合成更快的反应时间，使用的反应物、试剂和溶剂更少。然而，基于高效液相的自动化确实存在传统固相合成的固有缺陷。在开发基于高效液相和STICS方法的过程中取得了可喜的初步结果的基础上，这项提案旨在为自动化和监控合成生成一个用户友好的通用平台。这项提议分为四个具体目标，致力于：1)化学糖基化的新概念；2)高效液相辅助合成的所有方面的改进；3)作为固体载体的纳米孔材料的制备和应用；以及4)研究肿瘤相关标记物的合成和分析工具的开发。在完成拟议的研究后，我们预计将获得一个可靠和简单的自动化低聚糖合成平台。许多种类的化合物可以通过固体载体获得；因此，拟议的研究有望对所有科学家具有有价值的方法学和实用价值。几乎任何人只要接触到基本的高效液相设备，就应该能够进行自动合成和实时反应监测。使用这个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。

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.