HOST GUEST METALLOPROTEIN MIMICS

宿主客体金属蛋白模拟物

• 批准号: 6258794
• 负责人: JAMES W CANARY
• 金额: $ 0.04万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258794
• 关键词: biological products; biomedical equipment development; biomedical resource; biotechnology; proteins; technology /technique development

The goal of this project is the development of therapeutic agents for diseases that can be treated by inhibiting zinc hydrolytic enzymes, including rheumatoid and osteoarthritis, periodontitis, glaucoma, and cancer. The design of these agents requires a knowledge of (1) the mechanism of the enzyme and (2) the energies of binding interactions between the enzyme and an inhibitor. It is difficult to measure the contribution of an individual type of interaction in an enzyme due to its size and complexity. This proposal focuses on two zinc hydrolytic enzymes, carbonic anhydrase and carboxypeptidase A. It is believed that many other zinc enzymes are similar in structure and utilize similar mechanisms. Our approach to these problems is to design, synthesize, and study small molecule models of the enzymes to test mechanistic hypotheses for use for in drug design. The synthesis of the compounds requires characterization by various methods, including low and high resolution EI- and FAB-MS.

该项目的目标是开发治疗剂 对于可通过抑制锌水解 酶，包括类风湿和骨关节炎，牙周炎， 青光眼和癌症。 这些代理的设计需要知识 （1）酶的作用机制和（2）结合能 酶和抑制剂之间的相互作用。 很难 衡量一个单独类型的相互作用的贡献， 酶由于其大小和复杂性。 该提案侧重于两个 锌水解酶、碳酸酐酶和羧肽酶A。它 据信许多其它锌酶在结构上类似， 使用类似的机制。 我们解决这些问题的方法是 设计，合成和研究酶的小分子模型， 测试用于药物设计的机制假设。 合成 需要通过各种方法进行表征， 包括低和高分辨率EI-和FAB-MS。