SHIKIMATE-CHORISMATE PATHWAY

莽草酸-分支酸途径

• 批准号: 2175342
• 负责人: PAUL A BARTLETT
• 金额: $ 23.74万
• 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 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2175342
• 关键词: antibiotics; chemical synthesis; cyclic compound; drug design /synthesis /production; enzyme inhibitors; enzyme mechanism; ether hydrolase; isomerase; phosphorus oxygen lyase; shikimate; stereochemistry

Continuation of a broadly based bioorganic program to study some of the key enzymes in the shikimate-chorismate pathway is proposed. The major elements are the following: 1.5-Enolpyruvylshikimate-3-phosphate Synthase. We propose to continue our work on the synthesis of stabilized analogs of the tetrahedral intermediate and on the synthesis of this species itself; we will also study the mechanism and stereochemistry of the elimination step. 2.Chorismate Synthase. Through the use of isotopically labeled substrate analogs and of 5-deazaflavin, we will study the role of the flavin cofactor and the mechanism of the 1,4-elimination reaction catalyzed by this enzyme. 3.Chorismate Mutase. We expect to complete our study of this enzyme with the synthesis of ammonium and aziridinium inhibitor analogs and an investigation of an electronically perturbed substrate analog. 4.Dehydroquinate Synthase. We propose to resolve the remaining mechanistic issue, namely the extent of enzymatic involvement in the final step of the transformation, and to synthesize some potential suicide inhibitors of the enzyme. 5.Dehydroquinase. We will initiate a program to develop suicide inhibitors for this early enzyme in the pathway. 6.Isochorismate Synthase and Isochorismatase. We will initiate programs to develop inhibitors and reaction intermediate analogs for these enzymes of a branch pathway.

继续进行基础广泛的生物有机项目的一些重点研究