TRIPOD LIGANDS FOR ENZYME MODELS

用于酶模型的三脚架配体

• 批准号: 6417399
• 负责人: GERARD PARKIN
• 金额: $ 6.68万
• 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 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6417399
• 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）锌对于所有人都是必不可少的 生命形式，是人类第二丰富的痕量元素 身体。 相应地，锌参与了多种生物学 包括碳水化合物，脂质，蛋白质和核酸的过程 合成，调节和降解。 因此，锌是 缺乏障碍的有效增长和发展必不可少的要素 导致器官畸形。 为了能够充分理解 锌缺乏的后果，因此提出了可能的补救措施， 最重要的是了解锌的生物学化学。 目的 该提议的内容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 赤铁酶，羧肽酶，热解和肝酒脱氢酶。 具体而言，锌的生物无机化学将由 研究合成类似物的化学，即简单分子 旨在模仿活性位点的结构和功能 锌酶。 合成类似物更适合结构， 光谱学和机械研究比酶本身，因此 对这些系统的确定调查将允许大量见解 旨在确定酶的作用机理。 结果 这些研究可以显着提高我们对 锌的生物无机化学，因此可能是相当大的 在提供治愈疾病的理性基础上的重要性 锌不足。