ENZYME REACTORS FOR THE SYNTHESIS OF PEPTIDE INHIBITORS

用于合成肽抑制剂的酶反应器

• 批准号: 3501840
• 负责人: James B. West
• 金额: $ 4.04万
• 依托单位: BEND RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3501840
• 关键词: ACE inhibitors; angiotensin /renin /aldosterone hypertension; antihypertensive agents; bioreactors; cardiovascular disorder chemotherapy; drug design /synthesis /production; high performance liquid chromatography; nuclear magnetic resonance spectroscopy; peptide chemical synthesis; protease inhibitor; renin; synthetic peptide

Hypertension is one of the major health challenges facing researchers in pharmaceutical field today. Synthetic peptides that are inhibitors of renin and angiotensin-converting enzyme [ACE] have proved very successful in treating hypertension and have shown promise in treating other disease states. While the demand is high for synthetic peptides to treat hypertension and other disorders, available peptide-synthesis techniques have serious drawbacks. The drawbacks include racemization of components during coupling reactions, the high cost and potential environmental hazards posed by the coupling reagents used, and the expensive and time-consuming purification steps required after each coupling step. This project is directed at demonstrating the feasibility of an improved peptide-synthesis procedure. The process is based on a novel membrane- based enzyme reactor that overcome the disadvantages of conventional synthesis techniques. The objectives of this Phase I program are threefold: 1) to determine the operating conditions required for a membrane-based enzyme reactor for the continuous synthesis of a model peptide, 2) to construct the enzyme reactor, and 3) to test the performance of the system. Success in Phase I would lead to a Phase II program focused on the optimization and scale-up of the proposed process and investigation of additional applications.

高血压是研究人员面临的主要健康挑战之一， 今天的制药业 合成肽类，其为 肾素和血管紧张素转换酶（ACE）已被证明是非常成功的 并在治疗其它疾病中显示出前景 states. 虽然对合成肽治疗高血压和高血压的需求很高， 其他疾病，可用的肽合成技术有严重的 缺点. 缺点包括在制备过程中组分的外消旋化。 偶联反应，成本高，并带来潜在的环境危害 通过使用的偶联试剂，以及昂贵和耗时的 在每个偶联步骤之后需要纯化步骤。 该项目旨在证明改进的 肽合成程序。 这个过程是基于一种新的膜- 基于酶反应器，克服了传统的缺点， 合成技术 第一阶段计划的目标有三个方面：1）确定 所需的基于膜的酶反应器的操作条件， 模型肽的连续合成，2）构建酶 反应器，以及3）测试系统的性能。 第一阶段的成功 将导致第二阶段计划的重点是优化和扩大规模， 建议的程序和调查额外的应用程序。