SusChEM: Chemoenzymatic Methods for Efficient Synthesis of Glycolipids

SusChEM：高效合成糖脂的化学酶法

• 批准号: 1300449
• 负责人: Xi Chen
• 金额: $ 15万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1300449&HistoricalAwards=false
• 关键词: SusChEM; Chemoenzymatic; Methods; Efficient; Synthesis

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Xi Chen of the Department of Chemistry at the University of California-Davis will explore the development of chemoenzymatic synthesis and simple cartridge-purification methods for complex glycosphingolipids. The focus of the current project will be on neolacto-series glycosphingolipids with various lengths. While chemoenzymatic synthetic methods have been increasingly developed and used for producing oligosaccharides, less progress has been made in preparative-scale and large-scale synthesis of long and complex glycosphingolipids. This is mainly due to the limited access to suitable glycosyltransferases and sugar nucleotides as well as challenges in product purification. This work combines highly efficient glycosyltransferase-based one-pot multienzyme glycosylation systems with facile cartridge-purification schemes to allow the synthesis of complex glycosphingolipids with high yield, low cost, and in a short period of time from inexpensive monosaccharides, common nucleotides, and other simple starting materials. The process can be adapted to automated synthesis of glycolipids. The easy accessibility of glycolipids will provide essential probes and standards for basic research and greatly facilitate the understanding of their important roles and accelerate their therapeutic applications as cancer vaccines, cancer markers, and antimicrobial treatment. The proposed chemoenzymatic synthetic approaches and cartridge purification scheme are sustainable, as they use bioregenerable catalysts, a minimal amount of chemical reagents and organic solvents, and are environmentally friendly. This project will provide training to graduate students, undergraduate students, and high school students of diverse economic, gender, cultural, and ethnic backgrounds, allowing them to gain valuable skills, independence, and confidence in interdisciplinary research.

在这个由化学部化学合成项目资助的项目中，加州大学戴维斯分校化学系的陈曦教授将探索复杂鞘糖脂的化学酶法合成和简单的柱纯化方法的发展。当前项目的重点将是不同长度的新乳糖系列鞘糖脂。虽然化学酶合成方法已越来越多地开发并用于生产寡糖，但在长且复杂的鞘糖脂的制备规模和大规模合成方面取得的进展较少。这主要是由于合适的糖基转移酶和糖核苷酸的获取有限以及产品纯化方面的挑战。 这项工作将高效的基于糖基转移酶的一锅多酶糖基化系统与简便的柱纯化方案相结合，可以在短时间内从廉价的单糖、常见核苷酸和其他物质合成复杂的鞘糖脂，产量高、成本低。简单的起始材料。该工艺可适用于糖脂的自动化合成。糖脂的易获取性将为基础研究提供必要的探针和标准，极大地促进对其重要作用的理解，并加速其作为癌症疫苗、癌症标记物和抗菌治疗的治疗应用。所提出的化学酶合成方法和滤筒纯化方案是可持续的，因为它们使用生物可再生催化剂、最少量的化学试剂和有机溶剂，并且是环境友好的。该项目将为不同经济、性别、文化和种族背景的研究生、本科生和高中生提供培训，使他们在跨学科研究中获得宝贵的技能、独立性和信心。