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.

该项目的目的是开发治疗剂 对于可以通过抑制锌水解治疗的疾病 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）酶的机理和（2）结合的能量 酶与抑制剂之间的相互作用。 很难 测量单个类型的相互作用的贡献 酶的大小和复杂性。 该提议重点是两个 锌水解酶，碳酸酐酶和羧肽酶A 被认为许多其他锌酶在结构上相似， 利用类似的机制。 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 测试机械假设用于药物设计。 综合 这些化合物需要通过各种方法进行表征， 包括低分辨率EI-和Fab-MS。