Refinement and implementation of the automated oligosaccharide synthesizer

自动化寡糖合成仪的完善和实现

• 批准号: 9755447
• 负责人: ALEXEI V DEMCHENKO
• 金额: $ 48.61万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755447
• 关键词: Academia; Area; Attention; Automation; Biochemistry; Biological; Biological Sciences; Carbohydrate Chemistry; Carbohydrates; Chemicals; Chemistry; Communities; Complex; Computer Interface; Computer software; Development; Diagnostic; Discipline; Disease; Equipment; Evolution; Genomics; Goals; Government; Health; High Pressure Liquid Chromatography; Human; Individual; Industry; Knowledge; Laboratories; Libraries; Liquid Chromatography; Liquid substance; Manuals; Medical; Medicine; Methodology; Methods; Microarray Analysis; Mind; Monitor; Nature; Oligosaccharides; Organic Synthesis; Organism; Plant Resins; Polymers; Polysaccharides; Preparation; Procedures; Proteomics; Public Health; Reaction Time; Reagent; Reporting; Research; Research Personnel; Research Project Grants; Role; S Phase; Science; Scientist; Sialic Acids; Societies; Solid; Solvents; Specialist; Structure; System; Technology; Therapeutic; Therapeutic Agents; Thioglycosides; Time; Training; Vaccines; base; computer program; cost; detector; dietary supplements; experience; glycosylation; high standard; innovation; interest; programs; research and development; symposium; time use; user-friendly

Refinement and Implementation of the Automated Oligosaccharide Synthesizer 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, this proposal will focus on the introduction of an affordable and accessible automation platform that will enable both specialists and non- specialists to perform the synthesis of glycans. Current automated methods for the synthesis of oligosaccharides are highly sophisticated, operationally complex, and require significant user know-how. By contrast, high performance liquid chromatography (HPLC) equipment-based automation introduced by Demchenko and Stine represents a highly accessible method of synthesis. This is because many glycoscientists have operational knowledge of, and easy access to, HPLC equipment. The automated synthesis offers not only operational simplicity by delivering all reagents using standard autosamplers, but also convenient real-time reaction monitoring of every step using detectors and standard computer software and interface. We achieved faster reaction times using less reactant, reagent, and solvent than manual solid-phase synthesis. Building upon promising preliminary results, this proposal aims to generate a user-friendly, universal platform for automated and transformative synthesis of glycans. While the proposed automation approach has the potential to revolutionize glycan synthesis, practically every aspect of solid phase synthesis needs to be refined. This proposal is organized into four specific aims. The first three aims are dedicated to the refinement of inherent limitations of solid phase synthesis: 1) new affordable resins and the universal linker for solid phase synthesis; 2) new concepts for catalytic and stereocontrolled glycosylation; and 3) new methods for streamlined access to building blocks. The fourth aim is dedicated to the implementation of autosamplers as a mode for automation of the oligosaccharide synthesis. 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 many scientists. Investigators with access to standard HPLC equipment should be able to perform automated synthesis of glycan libraries using our reagent kits or easily interface with their existing methods and equipment. Synthesis of carbohydrates and other classes of biomolecules using this user-friendly, automated platform will accelerate discovery in many scientific disciplines and can significantly impact technology, society, the economy, and public health.

自动寡糖合成器的细化和实施 项目摘要 碳水化合物构成了所有生物体的基础，因此，无处不在 生物活性化合物和医学作为治疗剂。尽管一直对 碳水化合物的合成，这些分子的固有复杂性一致地捕获 许多科学家的注意，分离，化学或酶促合成的方法，分析和 碳水化合物的应用仍然很麻烦。越来越多的时间限制和成本限制 糖科学和糖原学的研究与发展呼吁开发快速，高效和 操作简单的过程。虽然这代表了一项艰巨的任务，但该提案将重点放在 引入负担得起且易于访问的自动化平台，该平台将使专家和非 专家执行聚糖的合成。 当前合成寡糖的自动化方法是高度复杂的，在操作上 复杂，需要大量的用户知识。相比之下，高性能液相色谱（HPLC） Demchenko和Stine引入的基于设备的自动化代表了一种高度可访问的方法 合成。这是因为许多糖基础主义者都有对HPLC的操作知识，并且容易访问 设备。自动合成不仅可以通过使用 标准的自动采样器，但也使用检测器对每个步骤进行方便的实时反应监视 标准的计算机软件和接口。我们使用较少的反应物，试剂和 溶剂比手动固相合成。在有希望的初步结果的基础上，该提案旨在 生成一个用户友好的通用平台，用于聚糖的自动化和变革性合成。 虽然提出的自动化方法有可能革新聚糖合成，但实际上是 固相合成的方面需要完善。该提议分为四个特定目标。第一个 三个目的是针对固相合成固有局限性的改进：1）新的负担得起 树脂和固相合成的通用接头； 2）催化和立体控制的新概念 糖基化； 3）简化访问构建块的新方法。第四个目标是针对 实施自动采样器作为寡糖合成自动化的模式。完成后 在拟议的研究中，我们希望获得一个可靠且简单的平台以进行自动化 寡糖合成。可以使用固体载体获得许多类别的化合物；因此， 预计拟议的研究对许多科学家来说具有宝贵的方法论和实际用途。调查人员 使用标准的HPLC设备，应该能够执行Glycan库的自动合成 使用我们的试剂套件或轻松与其现有方法和设备接口。合成 使用此用户友好，自动化平台将加速的碳水化合物和其他类别的生物分子 在许多科学学科中的发现，可以显着影响技术，社会，经济和 公共卫生。

项目成果

Facile and robust methods for the regioselective acylation of N-acetylneuraminic acid.

N-乙酰神经氨酸的区域选择性酰化的简便而可靠的方法。

• DOI: 10.1039/c8nj02795a
• 发表时间: 2018
• 期刊: New journal of chemistry = Nouveau journal de chimie
• 作者: Shadrick,Melanie;Yu,Charlene;Geringer,Scott;Ritter,Sean;Behm,Alexanndra;Cox,Abby;Lohman,Matt;DeMeo,Cristina
• 通讯作者: DeMeo,Cristina

Investigation of Glycosyl Nitrates as Building Blocks for Chemical Glycosylation: Investigation of Glycosyl Nitrates as Building Blocks for Chemical Glycosylation

硝酸糖基作为化学糖基化结构单元的研究： 硝酸糖基作为化学糖基化结构单元的研究

• DOI: 10.1002/ejoc.201801272
• 发表时间: 2018
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Wang, Tinghua;Singh, Yashapal;Stine, Keith J.;Demchenko, Alexei V.
• 通讯作者: Demchenko, Alexei V.

Synthesis of carbohydrate building blocks via regioselective uniform protection/deprotection strategies

• DOI: 10.1039/c9ob00573k
• 发表时间: 2019-05-28
• 期刊: ORGANIC & BIOMOLECULAR CHEMISTRY
• 影响因子: 3.2
• 作者: Wang, Tinghua;Demchenko, Alexei V.
• 通讯作者: Demchenko, Alexei V.

Triflic acid-mediated synthesis of thioglycosides

• DOI: 10.1039/c9ob01610d
• 发表时间: 2019-09-28
• 期刊: ORGANIC & BIOMOLECULAR CHEMISTRY
• 影响因子: 3.2
• 作者: Escopy, Samira;Singh, Yashapat;Demchenko, Alexei, V
• 通讯作者: Demchenko, Alexei, V

Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks

作为通用结构单元的 2-叠氮基-2-脱氧-和 2-乙酰氨基-2-脱氧-D-甘露糖衍生物的合成

• DOI: 10.1016/j.carres.2019.107900
• 发表时间: 2020
• 期刊: Carbohydrate Research
• 影响因子: 3.1
• 作者: Alex, Catherine;Visansirikul, Satsawat;Zhang, Yongzhen;Yasomanee, Jagodige P.;Codee, Jeroen;Demchenko, Alexei V.
• 通讯作者: Demchenko, Alexei V.