Automation of Neoglycoside Synthesis

新糖苷合成自动化

• 批准号: 7392967
• 负责人: charles r hutchinson
• 金额: $ 19.88万
• 依托单位: CENTROSE, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7392967
• 关键词: Address; Animals; Antibiotics; Antineoplastic Agents; Arts; Automation; Beds; Biological; Biological Factors; Cardiac; Caring; Chemistry; Classification; Communicable Diseases; Compatible; Computer software; Dental; Development; Drug Formulations; Elements; Facility Construction Funding Category; Funding Opportunities; Future; Heating; Legal patent; Libraries; Ligation; Malignant Neoplasms; Manuals; Marketing; Measures; Medical; Methods; Modeling; Modification; Monosaccharides; Operative Surgical Procedures; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Plants; Procedures; Process; Production; Property; Range; Reaction; Reagent; Reproducibility; Research; Research Design; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Solvents; Source; Specificity; Staging; System; Technology; Therapeutic; Therapeutic Agents; TimeLine; Translating; United States National Institutes of Health; base; cost; dosage; drug discovery; glycosylation; improved; manufacturing process; member; microbial; new technology; programs; prototype; reaction rate; research and development; scaffold; small molecule

DESCRIPTION (provided by applicant): The process of small molecule and natural product glycorandomization developed by Thorson and coworkers has been validated as one of the first simple, efficient and general glycosylation strategies for small molecule and macromolecular therapeutics. Given its broad utility and documented impact on improving the specificity, mechanism and ADME properties of drug leads, the glycorandomization technology platform is expected to revolutionize the future of drug discovery. Centrose, LLC, a company based upon this technology platform, will use the patented glycorandomization and neoglycorandomization technologies to develop breakthrough products to treat cancer with an anticipated future expansion into the infectious disease market. The ability to further accelerate and simplify the revolutionary glycorandomization process via automation will radically enhance the impact of glycorandomization upon the future of drug discovery. This phase I SBIR proposal specifically targets PA-06-012 (Manufacturing Processes of Medical, Dental, and Biological Technologies; SBIR R43/R44) and presents a systematic approach toward the development of a prototype (designated the `glycolator') for fully-automated neoglycorandomization drug discovery. Within the early Phase I timeline, we specifically seek to delineate the best reaction solvent, reaction heating, reaction mixing and product purification parameters compatible with our selected automation platform - the Gilson GX-271 ASPECTM. These elements will then be combined as the first fully automated `glycolator' and the later Phase I timeline specifically dedicated to assessing the utility of the glycolator for both library construction and preparative scale synthesis of representative neoglycosides. As a potential future Phase II study, we envision an expansion of this automated platform to encompass both automated upstream monosaccharide chemistries and automated downstream chemoselective ligation chemistries - both of which are anticipated to greatly enhance the competitive advantage of the glycorandomization drug discovery technology platform.

描述（由申请人提供）：Thorson 及其同事开发的小分子和天然产物糖随机化过程已被验证为小分子和大分子治疗的第一个简单、有效和通用的糖基化策略之一。鉴于其广泛的实用性和对改善先导药物的特异性、机制和 ADME 特性的影响，糖随机化技术平台有望彻底改变药物发现的未来。 Centrose, LLC 是一家基于该技术平台的公司，将利用获得专利的糖随机化和新糖随机化技术来开发治疗癌症的突破性产品，并预计未来将扩展到传染病市场。通过自动化进一步加速和简化革命性糖随机化过程的能力将从根本上增强糖随机化对未来药物发现的影响。这一第一阶段 SBIR 提案专门针对 PA-06-012（医疗、牙科和生物技术的制造工艺；SBIR R43/R44），并提出了一种开发用于全自动新糖随机化药物发现的原型（称为“糖化酶”）的系统方法。在第一阶段的早期时间表内，我们特别寻求与我们选择的自动化平台 - Gilson GX-271 ASPECTM 兼容的最佳反应溶剂、反应加热、反应混合和产品纯化参数。然后，这些元素将被组合为第一个完全自动化的“糖化器”，以及后来的第一阶段时间表，专门用于评估糖化器在文库构建和代表性新糖苷的制备规模合成中的效用。作为未来潜在的 II 期研究，我们设想扩展该自动化平台，以涵盖自动化上游单糖化学和自动化下游化学选择性连接化学 - 预计这两者将大大增强糖随机化药物发现技术平台的竞争优势。