TRIPOD LIGANDS FOR ENZYME MODELS

用于酶模型的三脚架配体

• 批准号: 2466487
• 负责人: GERARD PARKIN
• 金额: $ 20.14万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2466487
• 关键词: X ray crystallography; active sites; carbonate dehydratase; chemical structure function; chemical synthesis; enzyme model; enzyme substrate complex; ligands; metalloenzyme; nuclear magnetic resonance spectroscopy; receptor binding; stereochemistry; thermodynamics; zinc

DESCRIPTION: (Adapted from applicant's abstract) Zinc is essential to all forms of life and is the second most abundant trace element in the human body. Correspondingly, zinc participates in a wide variety of biological processes, which include carbohydrate, lipid, protein and nucleic acid synthesis, regulation, and degradation. Zinc is, therefore, an indispensable element for effective growth and development, with deficiency resulting in organ malformations. In order to be able to understand fully the consequences of zinc deficiency, and hence suggest possible remedies, it is most essential to understand the bioinorganic chemistry of zinc. The aim of this proposal is to define more fully the bioinorganic chemistry of zinc with respect to a selection of zinc enzymes, which include carbonic anhydrase, carboxypeptidase, thermolysis and liver alcohol dehydrogenase. Specifically, the bioinorganic chemistry of zinc will be delineated by studying the chemistry of synthetic analogs, i.e. simple molecules that are intended to mimic both the structure and function of the active sites of zinc enzymes. Synthetic analogs are more amenable to structural, spectroscopic, and mechanistic studies than the enzymes themselves, so that definitive investigations of these systems will allow considerable insight into the mechanism of action of the enzymes to be ascertained. The results of these studies could significantly improve our understanding of the bioinorganic chemistry of zinc and consequently could be of considerable importance in providing a rational basis of curing diseases resulting from zinc deficiency.

描述：（改编自申请人的摘要）锌对所有人来说都是必需的 生命形式，是人体中第二丰富的微量元素 身体。 相应地，锌参与多种生物活性。 过程，包括碳水化合物、脂质、蛋白质和核酸 合成、调节和降解。 因此，锌是一种 有效生长和发育不可或缺的元素，缺乏 导致器官畸形。 为了能够充分理解 缺锌的后果，因此提出可能的补救措施， 对于了解锌的生物无机化学至关重要。 目的 该提案的目的是更全面地定义锌的生物无机化学 关于锌酶的选择，其中包括碳酸 脱水酶、羧肽酶、热解酶和肝乙醇脱氢酶。 具体来说，锌的生物无机化学将被描述为 研究合成类似物的化学，即简单分子 旨在模拟活性位点的结构和功能 锌酶。 合成类似物更适合结构， 光谱和机理研究比酶本身更重要，因此 对这些系统的明确研究将带来相当多的见解 进入待确定的酶的作用机制。 结果 这些研究可以显着提高我们对 锌的生物无机化学，因此可能具有相当大的作用 为治疗由以下疾病引起的疾病提供合理的基础非常重要 缺锌。