STUDIES IN THE SHIKIMATE-CHORISMATE PATHWAY

莽草酸-分支酸途径的研究

• 批准号: 3276375
• 负责人: PAUL A BARTLETT
• 金额: $ 17.92万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3276375
• 关键词: antibiotics; chemical synthesis; cyclic compound; drug design /synthesis /production; shikimate; stereochemistry

A broadly based bioorganic program for the study of some of the key enzymes in the shikimate-chorismate pathway is outlined. The key elements are the following: 1. Chorismate mutase: New transition state analog inhibitors will be synthesized and evaluated; a synthesis of chorismic acid itself will be completed. 2. 3-Dehydroquinate synthase: The stereochemistry of the individual steps in the enzymic transformation will be determined by stereoselective synthesis of a key intermediate; blocked-substrate as well as transition state analog inhibitors will be synthesized and evaluated. 3. Chorismate synthetase: An allylic isomer of the natural substrate will be synthesized and evaluated as an alternative substrate or inhibitor. 4. 5-Enolpyruvylshikimate-3-phosphate synthase: The postulated tetrahedral adduct will be synthesized and its enzymatic conversion to product evaluated; transition state and multisubstrate analog inhibitors will also be synthesized. 5. Prephenate dehydratase: A series of sulfoxide and sulfilimine analogs of prephenate will be synthesized and evaluated as transition state analog or suicide inhibitors. 6. A number of other analogs of intermediates in the shikimate-chorismate pathway are proposed as substrates and inhibitors.

一个基础广泛的生物有机程序，用于研究一些关键的酶