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本文引用的文献

1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
Exploring the chemical space around 8-mercaptoguanine as a route to new inhibitors of the folate biosynthesis enzyme HPPK.探索 8-巯基鸟嘌呤周围的化学空间，寻找叶酸生物合成酶 HPPK 的新抑制剂。
PLoS One. 2013;8(4):e59535. doi: 10.1371/journal.pone.0059535. Epub 2013 Apr 2.
3
Bisubstrate analog inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: new lead exhibits a distinct binding mode.6-羟甲基-7,8-二氢蝶啶磷酸核糖基转移酶的双底物类似物抑制剂：新的先导化合物具有独特的结合模式。
Bioorg Med Chem. 2012 Jul 15;20(14):4303-9. doi: 10.1016/j.bmc.2012.05.060. Epub 2012 Jun 6.
4
Catalysis and sulfa drug resistance in dihydropteroate synthase.二氢叶酸合成酶中的催化作用和磺胺类药物耐药性。
Science. 2012 Mar 2;335(6072):1110-4. doi: 10.1126/science.1214641.
5
Structure of S. aureus HPPK and the discovery of a new substrate site inhibitor.金黄色葡萄球菌 HPPK 的结构和新型底物结合位点抑制剂的发现。
PLoS One. 2012;7(1):e29444. doi: 10.1371/journal.pone.0029444. Epub 2012 Jan 19.
6
Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties.6-羟甲基-7,8-二氢蝶啶磷酸核糖基转移酶的双底物类似物抑制剂：具有改进性能的新设计。
Bioorg Med Chem. 2012 Jan 1;20(1):47-57. doi: 10.1016/j.bmc.2011.11.032. Epub 2011 Nov 23.
7
From experimental design to validated hits a comprehensive walk-through of fragment lead identification using surface plasmon resonance.从实验设计到验证的活性化合物：使用表面等离子体共振进行片段先导物识别的全面指南
Methods Enzymol. 2011;493:169-218. doi: 10.1016/B978-0-12-381274-2.00008-X.
8
Crystal structure of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase•dihydropteroate synthase bifunctional enzyme from Francisella tularensis.弗氏志贺菌 6-羟甲基-7,8-二氢蝶呤焦磷酸激酶•二氢蝶酸合酶双功能酶的晶体结构
PLoS One. 2010 Nov 30;5(11):e14165. doi: 10.1371/journal.pone.0014165.
9
Exploring minimal biotinylation conditions for biosensor analysis using capture chips.探索使用捕获芯片进行生物传感器分析的最小生物素化条件。
Anal Biochem. 2010 Aug;403(1-2):30-5. doi: 10.1016/j.ab.2010.03.044. Epub 2010 Apr 4.
10
Structural studies of pterin-based inhibitors of dihydropteroate synthase.蝶呤类二氢叶酸合成酶抑制剂的结构研究。
J Med Chem. 2010 Jan 14;53(1):166-77. doi: 10.1021/jm900861d.

6-羟甲基-7,8-二氢蝶呤焦磷酸激酶新型抑制剂的鉴定、分析及基于结构的开发

The identification, analysis and structure-based development of novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.

作者信息

Yun Mi-Kyung, Hoagland Daniel, Kumar Gyanendra, Waddell M Brett, Rock Charles O, Lee Richard E, White Stephen W

机构信息

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

出版信息

Bioorg Med Chem. 2014 Apr 1;22(7):2157-65. doi: 10.1016/j.bmc.2014.02.022. Epub 2014 Feb 25.

DOI:10.1016/j.bmc.2014.02.022
PMID:24613625
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4269157/
Abstract

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is an essential enzyme in the microbial folate biosynthetic pathway. This pathway has proven to be an excellent target for antimicrobial development, but widespread resistance to common therapeutics including the sulfa drugs has stimulated interest in HPPK as an alternative target in the pathway. A screen of a pterin-biased compound set identified several HPPK inhibitors that contain an aryl substituted 8-thioguanine scaffold, and structural analyses showed that these compounds engage the HPPK pterin-binding pocket and an induced cryptic pocket. A preliminary structure activity relationship profile was developed from biophysical and biochemical characterizations of derivative molecules. Also, a similarity search identified additional scaffolds that bind more tightly within the HPPK pterin pocket. These inhibitory scaffolds have the potential for rapid elaboration into novel lead antimicrobial agents.

摘要

6-羟甲基-7,8-二氢蝶呤焦磷酸激酶（HPPK）是微生物叶酸生物合成途径中的一种关键酶。该途径已被证明是抗菌药物研发的一个理想靶点，但包括磺胺类药物在内的常见治疗药物出现广泛耐药性，激发了人们对HPPK作为该途径替代靶点的兴趣。对一组偏向蝶呤的化合物进行筛选，鉴定出了几种含有芳基取代8-硫鸟嘌呤支架的HPPK抑制剂，结构分析表明这些化合物与HPPK蝶呤结合口袋和一个诱导产生的隐蔽口袋相互作用。通过对衍生分子的生物物理和生化表征，建立了初步的构效关系图谱。此外，相似性搜索还识别出了能更紧密结合在HPPK蝶呤口袋内的其他支架。这些抑制性支架有潜力快速发展成为新型抗菌先导药物。