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利用酶亚位点的原核生物UDP-吡喃半乳糖变位酶的强效配体。

Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite.

作者信息

Dykhuizen Emily C, Kiessling Laura L

机构信息

Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

出版信息

Org Lett. 2009 Jan 1;11(1):193-6. doi: 10.1021/ol802094p.

DOI:10.1021/ol802094p
PMID:19067595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3010353/
Abstract

UDP-galactopyranose mutase (UGM or Glf), which catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose, is implicated in the viability and virulence of multiple pathogenic microorganisms. Here we report the synthesis of high-affinity ligands for UGM homologues from Klebsiella pneumoniae and Mycobacterium tuberculosis. The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site.

摘要

UDP-吡喃半乳糖变位酶(UGM或Glf)催化UDP-吡喃半乳糖和UDP-呋喃半乳糖的相互转化,与多种致病微生物的生存能力和毒力有关。在此,我们报告了肺炎克雷伯菌和结核分枝杆菌UGM同源物的高亲和力配体的合成。这些化合物的效力源于它们能够同时进入底物结合口袋和相邻位点。

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本文引用的文献

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J Am Chem Soc. 2008 May 28;130(21):6706-7. doi: 10.1021/ja8018687. Epub 2008 May 1.
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The cell-wall core of Mycobacterium tuberculosis in the context of drug discovery.药物研发背景下的结核分枝杆菌细胞壁核心
Curr Top Med Chem. 2007;7(5):475-88. doi: 10.2174/156802607780059763.
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Synthesis and analysis of substrate analogues for UDP-galactopyranose mutase: implication for an oxocarbenium ion intermediate in the catalytic mechanism.UDP-吡喃半乳糖变位酶底物类似物的合成与分析:对催化机制中氧鎓离子中间体的启示
Org Lett. 2007 Mar 1;9(5):879-82. doi: 10.1021/ol0631408. Epub 2007 Feb 1.
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Chem Biol. 2006 Aug;13(8):825-37. doi: 10.1016/j.chembiol.2006.06.007.
5
Exploring the mechanism of binding of UDP-galactopyranose to UDP-galactopyranose mutase by STD-NMR spectroscopy and molecular modeling.通过STD-NMR光谱法和分子建模探索UDP-吡喃半乳糖与UDP-吡喃半乳糖变位酶的结合机制。
Biochemistry. 2005 Nov 1;44(43):14080-9. doi: 10.1021/bi0513406.
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Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents.新型抗结核药物硝基呋喃酰胺的合成与评价
J Med Chem. 2004 Oct 7;47(21):5276-83. doi: 10.1021/jm049972y.
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Synthesis of novel ammonium and selenonium ions and their evaluation as inhibitors of UDP-galactopyranose mutase.新型铵离子和硒离子的合成及其作为UDP-吡喃半乳糖变位酶抑制剂的评价。
Carbohydr Res. 2004 Sep 13;339(13):2205-17. doi: 10.1016/j.carres.2004.07.012.
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Efficient synthesis of a nucleoside-diphospho-exo-glycal displaying time-dependent inactivation of UDP-galactopyranose mutase.核苷二磷酸外糖醛的高效合成及其对UDP-吡喃半乳糖变位酶的时间依赖性失活作用
Chem Commun (Camb). 2004 May 21(10):1216-7. doi: 10.1039/b402469a. Epub 2004 Apr 23.
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Synthesis and inhibition properties of conformational probes for the mutase-catalyzed UDP-galactopyranose/furanose interconversion.用于变位酶催化的UDP-吡喃半乳糖/呋喃半乳糖相互转化的构象探针的合成及抑制特性
Chemistry. 2003 Dec 5;9(23):5888-98. doi: 10.1002/chem.200305141.