I-Corps: An efficient enzymatic synthesis method for biomanufacturing of nucleoside analogues

I-Corps：一种用于核苷类似物生物制造的高效酶促合成方法

• 批准号: 1339044
• 负责人: Zvi Kelman
• 金额: $ 5万
• 依托单位: University of Maryland, College Park
• 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: 2013-04-15 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1339044&HistoricalAwards=false
• 关键词: Corps; efficient; enzymatic; synthesis; method

Nucleoside mimics and their conjugates (referred to as nucleoside analogues or "NAs") have diverse applications ranging from anti-viral and anti-tumor agents to nutritional supplements. Current chemical approaches for the synthesis of NAs are time consuming, expensive, and inefficient. Recently, researchers developed an enzyme-assisted biochemical synthesis of NAs in high yield and in a one-pot, single step reaction. The goals of the I-Corps proposal are to develop this into a robust biomanufacturing process and explore the chemical diversity of NAs that can be synthesized using this enzymatic approach. Researchers envision the enzymatic aqueous-based synthesis of NAs as the core technology for the manufacture of NAs that is inexpensive, rapid, highly efficient, and stereo selective. The process would also be an environmentally-friendly alternative to the currently available chemical approaches which generate large quantities of chemical waste.Current chemical synthesis methods to make NAs are multi step, time consuming and generate significant chemical waste. This limits the scope of research and development of NAs as potential therapeutic agents, diagnostic tools, biochemical probes, and nutritional supplements. Using enzymatic reaction in aqueous base will produce no waste and thus help the environment. The adoptability of the proposed method for high-throughput screening of the chemical space of the small molecules that can be conjugated to the NAs greatly enhances the search for highly effective NAs. NAs are used in the treatment of global epidemics such as HIV and HCV. There is an unmet need to produce anti-viral drugs at a cheaper price to cater to the third world countries. By using cost effective enzymatic synthesis of NAs, one can imagine mass production of these drugs at affordable prices.

核苷模拟物及其结合物（称为核苷类似物或“ NAS”）具有不同的应用，从抗病毒和抗肿瘤剂到营养补充剂。当前合成NA的化学方法是耗时，昂贵且效率低下的。最近，研究人员开发了一种酶辅助的生化合成，以高产量和一锅单步反应中NAS的生化合成。 I-Corps提案的目标是将其发展为强大的生物制造过程，并探索可以使用这种酶促方法合成的NA的化学多样性。研究人员设想了基于酶水的NAS合成NAS作为制造NAS的核心技术，该NA是廉价，快速，高效和立体声选择性的。该过程也将是当前可用的化学方法的环保替代品，这些化学方法产生了大量的化学废物。使NAS的流动化学合成方法是多步骤，耗时的，并且消耗量并产生大量的化学废物。这限制了NAS作为潜在治疗剂，诊断工具，生化探针和营养补充剂的研究和开发范围。在水基中使用酶促反应将不会产生浪费，从而有助于环境。提出的对小分子的化学空间进行高通量筛查的方法的可采用性，可以与NAS结合使用，从而大大增强了人们对高效NAS的搜索。 NAS用于治疗全球流行病，例如HIV和HCV。不满意以更便宜的价格生产抗病毒药物来迎合第三世界国家。通过使用成本有效的NAS酶合成，可以想象以可承受的价格大规模生产这些药物。