1-脱氧-D-木酮糖-5-磷酸还原异构酶的研究：氟化底物类似物的合成与评价

Study of 1-deoxy-D-xylulose-5-phosphate reductoisomerase: synthesis and evaluation of fluorinated substrate analogues.

作者信息

Wong Alexander, Munos Jeffrey W, Devasthali Vidusha, Johnson Kenneth A, Liu Hung-Wen

机构信息

Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.

出版信息

Org Lett. 2004 Sep 30;6(20):3625-8. doi: 10.1021/ol048459b.

DOI:10.1021/ol048459b

PMID:15387564

Abstract

[reaction: see text] 1-deoxy-D-xylulose-5-phosphate (DXP) reductoisomerase is a NADPH-dependent enzyme catalyzing the conversion of DXP to methyl-D-erythritol 4-phosphate (MEP). In this study, each of the hydroxyl groups in DXP and one of its C-1 hydrogen atoms, were separately replaced with a fluorine atom and the effect of the substitution on the catalytic turnover was examined. It was found that the 1-fluoro-DXP is a poor substrate, while both 3- and 4-fluoro-DXP behave as noncompetitive inhibitors.

摘要

[反应：见正文] 1-脱氧-D-木酮糖-5-磷酸（DXP）还原异构酶是一种依赖NADPH的酶，催化DXP转化为甲基-D-赤藓糖醇4-磷酸（MEP）。在本研究中，DXP中的每个羟基及其C-1氢原子之一分别被氟原子取代，并研究了取代对催化周转的影响。发现1-氟-DXP是一种不良底物，而3-氟-DXP和4-氟-DXP均表现为非竞争性抑制剂。