Computational Simulations of the Interactions between Acetyl-Coenzyme-A Carboxylase and Clodinafop: Resistance Mechanism Due to Active and Nonactive Site Mutations
作者：
Zhu, Xiao-Lei;Hao, Ge-Fei;Zhna, Chang-Guo;Yang, Guang-Fu
* （ 期刊：
Journal of Chemical Information and Modeling ,2009年49(8):1936-1943 ISSN：1549-9596
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Hao, Ge-Fei] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Peoples R China.;[Zhan, Chang-Guo] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Peoples R China.
会议名称：
International conference of molecular simulations and applied informatics technologies
会议时间：
2010-01-01
会议地点：
Wuhan(CN)
会议论文集名称：
The 5th International conference of molecular simulations and applied informatics technologies : [Life science articles proceedings]
摘要：
Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase;EC 6.4.1.2) herbicides represent a major problem for the sustainable development of modern agriculture. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) calculations, have been carried out to uncover the detailed molecular mechanism of Alopecurus myosuroides resistance to clodinafop, a commercial herbicide targeting ACCase. All the computational model and energetic results indicated that W374C, I388N, D425G, and G443A mutations have great effects on the conformational change of the binding pocket and the hydrogen-bonding interactions. The n-n interaction between ligand and the residue of Phe377 and Tyr161′, playing an important contribution to the binding affinity, were decreased after mutations. In addition, the hydrogen-bonding interactions between clodinafop and the residues (He 158' and Ala54′) disappeared or decreased significantly upon mutation. As a result, the mutant-type ACCase has a lower affinity for the inhibitor binding than the wild-type enzyme, which accounts for the molecular basis of herbicidal resistance. The structural and mechanistic insights obtained from the present study will provide a valuable clue for future designing of a promising inhibitor to reduce drug resistance associated with both active and nonactive site mutations. ©2009 American Chemical Society.
语种：
英文
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取代苯氧基***并嘧啶类化合物的合成及除草活性研究
期刊：
农药学学报 ,2009年11(1):31-35 ISSN：1008-7303
作者机构：
[杨光富; 陈琼; 刘玉超; 张明智] 华中师范大学
关键词：
1,2,4-***并[1,5-a]嘧啶;合成;除草活性
摘要：
以砜基取代的嘧啶为关键中间体,设计合成了17个新型取代苯氧基1,2,4-***并[1,5-a]嘧啶类衍生物,通过元素分析、MS和~1H NNIR对所合成的化合物进行了结构表征.初步生物活性测定结果表明,100 mg/L浓度下部分化合物对6种测试靶标均表现出较好的抑制活性,盆栽复筛试验显示在150 g/hm~2剂量下,5个化合物表现出较好的除草活性和持效性.
语种：
中文
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Bisbenzimidazole to benzobisimidazole: from binding B-form duplex DNA to recognizing different modes of telomere G-quadruplex
作者：
Huang, Jing;Li, Guorui;Wu, Zhiguo;Song, Zhibin;Zhou, Yangyang;...
期刊：
Chemical Communications ,2009年(8):902-904 ISSN：1359-7345
通讯作者：
Zhou, Xiang
作者机构：
[Li, Guorui; Zhou, Yangyang; Huang, Jing; Song, Zhibin; Shuai, Liang; Zhou, Xiang; Wu, Zhiguo; Weng, Xiaocheng] Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.;[Yang, Guangfu] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan, Peoples R China.
通讯机构：
[Zhou, Xiang] W;Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.
摘要：
A bisbenzimidazole was discovered to bind helix DNA, while related benzobisimidazole derivatives were found to bind and induce different G-quadruplex isomers.
语种：
英文
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苯并噻唑取代的***啉酮类衍生物的合成及除草活性
作者机构：
[杨光富; 江黎黎; 骆焱平; 陈琼] 农药与化学生物学教育部重点实验室 华中师范大学化学学院 武汉 430079;[骆焱平] 海南大学环境与植物保护学院 儋州 571737
会议名称：
中国化学会第六届有机化学学术会议
会议时间：
2009-8-1
会议地点：
西安
会议主办单位：
中国化学会
会议论文集名称：
中国化学会第六届有机化学学术会议论文集
语种：
中文
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Understanding the mechanism of drug resistance due to a codon deletion in protoporphyrinogen oxidase through computational modeling
作者：
Hao, Ge-Fei;Zhu, Xiao-Lei;Ji, Feng-Qin;Zhang, Li;Yang, Guang-Fu
* （ ;...
期刊：
JOURNAL OF PHYSICAL CHEMISTRY B ,2009年113(14):4865-4875 ISSN：1520-6106
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Ji, Feng-Qin; Zhang, Li; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Zhan, Chang-Guo] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
会议名称：
International conference of molecular simulations and applied informatics technologies
会议时间：
2010-01-01
会议地点：
Wuhan(CN)
会议论文集名称：
The 5th International conference of molecular simulations and applied informatics technologies : [Life science articles proceedings]
摘要：
Protoporphyrinogen oxidase (PPO;EC 1.3.3.4) is the last common enzyme for the enzymatic transformation of protoporphyrinogen-IX to protoporphyrin-IX, which is the key common intermediate leading to heme and chlorophyll. Hence, PPO has been identified as one of the most importance action targets for the treatment of some important diseases including cancer and variegated porphyria (VP). In the agricultural field, PPO inhibitors have been used as herbicides for many years. Recently, a unique drug resistance was found to be associated with a nonactive site residue (Gly210) deletion rather than substitution in A. tuberculatus PPO. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) calculations, have been carried out to uncover the detailed molecular mechanism of drug resistance associated with Gly210 deletion. Although Gly210 in the wild-type A. tuberculatus PPO has no direct interaction with the inhibitors, all the computational models and energetic results indicated that Gly210 deletion has great effects on the hydrogen-bonding network and the conformational change of the binding pocket. An interchain hydrogen bond between Gly210 with Ser424, playing an important role in stabilizing the local conformation of the wild-type enzyme, disappeared after Gly210 deletion. As a result, the mutant-type PPO has a lower affinity than the wild-type enzyme, which accounts for the molecular mechanism of drug resistance. The structural and mechanistic insights obtained from the present study provide a new starting point for future rational design of novel PPO inhibitors to overcome drug resistance associated with Gly210 deletion. ©2009 American Chemical Society.
语种：
英文
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4-取代芳基亚胺基-1,2,4-***-2-硫醚类化合物的合成及生物活性
作者机构：
[杨光富; 刘祖明; 赵培亮] 农药与化学生物学教育部重点实验室 华中师范大学化学学院 武汉 430079;[赵培亮] 南方医科大学药学院 广州 510515
会议名称：
中国化学会第六届有机化学学术会议
会议时间：
2009-8-1
会议地点：
西安
会议主办单位：
中国化学会
会议论文集名称：
中国化学会第六届有机化学学术会议论文集
语种：
中文
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The First Example of a Regioselective Biginelli-Like Reaction Based on 3-Alkylthio-5-amino-1,2,4-triazole
作者：
Chen, Qiong;Jiang, Li-Li;Chen, Chao-Nan;Yang, Guang-Fu
（ 期刊：
Journal of Heterocyclic Chemistry ,2009年46(2):139-148 ISSN：0022-152X
通讯作者：
Yang, GF
作者机构：
[Yang, Guang-Fu; Chen, Qiong; Jiang, Li-Li; Chen, Chao-Nan] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, GF ] ;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
The three‐component condensation of 3‐amino‐5‐alkylthio‐1,2,4‐triazoles with aromatic aldehydes and β‐ketoester was studied to develop a regioselective Biginelli‐like reaction. The results indicated that the reaction solvent and the properties of the β‐ketoester component displayed great influence on the regioselectivity. This is the first report about the regioselectivity of the aminotriazole‐based Biginelli‐like reaction. J. Heterocyclic Chem., (2009).
语种：
英文
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Axially 4,4′-di-tert-butyl TunePhos-type chiral diphosphine ligand: synthesis and applications in asymmetric hydrogenation
作者：
Wang, Chun-Jiang
* ;Wang, Chu-Bei;Chen, Dong;Yang, Guangfu
（ ;Wu, Zhengshun;...
期刊：
Tetrahedron Letters ,2009年50(9):1038-1040 ISSN：0040-4039
通讯作者：
Wang, Chun-Jiang
作者机构：
[Wang, Chun-Jiang; Wang, Chu-Bei; Chen, Dong] Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.;[Yang, Guangfu; Wang, Chu-Bei; Wu, Zhengshun] Cent China Normal Univ, Dept Chem, Wuhan 430079, Peoples R China.;[Yang, Guangfu; Wang, Chu-Bei; Wu, Zhengshun] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol CCNU, Wuhan 430079, Peoples R China.;[Zhang, Xumu] Rutgers State Univ, Dept Pharmaceut Chem, Piscataway, NJ 08854 USA.;[Zhang, Xumu] Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA.
通讯机构：
[Wang, Chun-Jiang] W;Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.
摘要：
Axially 4,4'-di-tert-butyl TunePhos-type chiral diphosphine ligand was designed and synthesized by means of central-to-axial chirality transfer. Up to 99% and 98% ee have been achieved in Ru-catalyzed hydrogenation of beta-alkyl and beta-aryl-substituted beta-keto esters, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
语种：
英文
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Supramolecular rhombic grids formed from bimolecular building blocks
作者：
She, Neng-Fang
（ ;Gao, Meng;Meng, Xiang-Gao;Yang, Guang-Fu
（ ;Elemans, Johannes A A W;...
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY ,2009年131(33):11695-11697 ISSN：0002-7863
作者机构：
[She, Neng-Fang; Yang, Guang-Fu; Wu, An-Xin; Gao, Meng; Meng, Xiang-Gao] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Elemans, Johannes A A W] Radboud Univ Nijmegen, Inst Mol & Mat, NL-6525 ED Nijmegen, Netherlands.;[Isaacs, Lyle] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
通讯机构：
[Wu, An-Xin] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
(Figure Presented) A programmed assembly process produces rhombic grid networks from compounds L1-L4 in the crystal by π-π stacking interactions that generate a bimolecular grid synthon, which undergoes further NH⋯N hydrogen-bond-mediated assembly. © 2009 American Chemical Society.
语种：
英文
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Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations
作者：
Zhang, Li;Hao, Ge-Fei;Tan, Yin;Xi, Zhen* ;Huang, Ming-Zhi;...
期刊：
Bioorganic & Medicinal Chemistry ,2009年17(14):4935-4942 ISSN：0968-0896
通讯作者：
Xi, Zhen
作者机构：
[Yang, Guang-Fu; Zhang, Li; Tan, Yin; Hao, Ge-Fei] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Xi, Zhen; Tan, Yin] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;[Huang, Ming-Zhi] Hunan Res Inst Chem Ind, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Xi, Zhen] N;Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
关键词：
Bioactive conformation;DFT;Molecular dynamic simulations;PPO;QSAR
摘要：
Bioactive conformation of drugs is one of the key points for understanding the ligand-receptor interactions. In the present study, by combining density functional theory-based (DFT-based) conformation analysis with quantitative structure-activity relationship analysis (QSAR), we developed successfully a new approach (DFT/QSAR) to carry out bioactive conformation analyses for a series of 25 cyclic imide derivatives as protoporphyrinogen oxidase (PPO) inhibitors. Further potential energy surface scan, molecular docking and molecular dynamic simulation calculations validated that the DFT/QSAR-derived conformation is indeed very similar to the 'real' bioactive conformation. We believe the DFT/QSAR approach provides a simple alternative for the bioactive conformation of small molecules, especially in the case that the three-dimensional structure of protein is unknown. © 2009 Elsevier Ltd. All rights reserved.
语种：
英文
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Synthesis and antitumor activity of novel dithiocarbamate substituted chromones
作者：
Huang, Wei;Ding, Yu;Miao, Yan;Liu, Ming-Zhen;Li, Yan* ;...
期刊：
European Journal of Medicinal Chemistry ,2009年44(9):3687-3696 ISSN：0223-5234
通讯作者：
Li, Yan
作者机构：
[Yang, Guang-Fu; Huang, Wei; Miao, Yan; Liu, Ming-Zhen; Ding, Yu] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Li, Yan] Wuhan Univ, Zhongnan Hosp, Ctr Canc, Wuhan 430072, Peoples R China.
通讯机构：
[Li, Yan] W;Wuhan Univ, Zhongnan Hosp, Ctr Canc, Wuhan 430072, Peoples R China.
关键词：
Flavonoids;Chromone;Dithiocarbamate;Antitumor activity
摘要：
A series of chromone derivatives bearing diverse dithiocarbamate moieties were designed and synthesized via a three-component reaction protocol. Their in vitro antitumor activities were evaluated by MTT method against HCCLM-7, Hela, MDA-MB-435S, SW-480, Hep-2 and MCF-7. Two compounds (3-chloro-4-oxo-4H-chromen-2-yl)methyl piperidine-1-carbodithioate (Iq) and (6-chloro-4-oxo-4H-chromen-3-yl)methyl piperidine-1-carbodithioate (IIu), were identified as the most promising candidate due to their high potency and broad-spectrum. Further flow-activated cell sorting analysis revealed that compounds Iq and IIu arrest the cell cycle of SW-480 and MDA-MB-435s both in G2/M phase with dose-dependent effect and might display apoptosis-inducing effect on these tumor cell lines. © 2009 Elsevier Masson SAS. All rights reserved.
语种：
英文
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Design and synthesis of N-2,6-difluorophenyl-5-methoxyl-1,2,4-triazolo[1,5-a]-pyrimidine-2-sulfonamide as acetohydroxyacid synthase inhibitor
作者：
Chen, Chao-Nan;Lv, Li-Li;Ji, Feng-Qin;Chen, Qiong;Xu, Hui;...
期刊：
Bioorganic & Medicinal Chemistry ,2009年17(8):3011-3017 ISSN：0968-0896
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Ji, Feng-Qin; Lv, Li-Li; Chen, Qiong; Xu, Hui; Chen, Chao-Nan] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Xi, Zhen; Niu, Cong-Wei] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词：
Triazolopyrimidine-2-sulfonamide;Herbicide;Acetohydroxyacid synthase inhibitor
摘要：
Triazolopyrimidine-2-sulfonamide belongs to a herbicide group called acetohydroxyacid synthase inhibitors. With the aim to discover new triazolopyrimidine sulfonanilide compounds with high herbicidal activity and faster degradation rate in soil, the methyl group of Flumetsulam (FS) was modified into a methoxy group to produce a new herbicidal compound, N-2,6-difluorophenyl-5-methoxy-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide (experimental code: Y6610). The enzymatic kinetic results indicated that compound Y6610 and FS have ki values of 3.31 × 10-6 M and 3.60 × 10-7 M against Arabidopsis thaliana AHAS, respectively. The 10-fold lower enzyme-inhibiting activity of Y6610 was explained rationally by further computational simulations and binding free energy calculations. In addition, compound Y6610 was found to display the same level in vivo post-emergent herbicidal activity as FS against some broad-leaf weeds and good safety to rice, maize, and wheat at the dosages of 75-300 g ai/ha. Further determination of the half-lives in soil revealed that the half-life in soil of Y6610 is 3.9 days shorter than that of FS. The experimental results herein showed that compound Y6610 could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study. © 2009 Elsevier Ltd. All rights reserved.
语种：
英文
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新型非拟肽磺胺类HIV蛋白酶抑制剂Darunavir的研究进展
期刊：
有机化学 ,2008年28(9):1545-1552 ISSN：0253-2786
通讯作者：
Hao Ge-Fei
作者机构：
[杨光富; 郝格非] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Hao Ge-Fei] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
HIV蛋白酶抑制剂;艾滋病;抗性突变
摘要：
综述新型非拟肽磺胺类人类免疫缺陷病毒（HIV）蛋白酶抑制剂Darunavir（TMC-114）的发现，抗病毒的活性，分子模拟以及结构优化的研究进展．Darunavir不但对野生型的HIV蛋白酶有很好的抑制活性，而且对多种抗性突变的HIV蛋白酶也有良好的活性，是针对耐药性HIV所开发的新药．
语种：
中文
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含肟醚的新型四唑啉酮衍生物的合成及除草活性研究
期刊：
有机化学 ,2008年28(9):1561-1565 ISSN：0253-2786
通讯作者：
Luo Yan-Ping
作者机构：
[杨光富; 骆焱平; 陈琼; 龚青] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[骆焱平] Hainan Univ, Coll Environm & Plant Protect, Danzhou 571737, Peoples R China.
通讯机构：
[Luo Yan-Ping] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
肟醚;四唑啉酮;除草活性
摘要：
1-（4-氯苯基）-1，4-二氢-四唑-5-酮（1）与氯丙酮反应生成1-（4-氯苯基）-4-（2-氧代丙基）-1，4-二氢-四唑-5-酮（2）．中间体2、盐酸羟胺和卤化物通过三组分一锅法合成了目标化合物3．初步生物活性测试结果表明：目标化合物3具有较好的除草活性．
语种：
中文
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双语有机化学研究型教学的探索
期刊：
高等继续教育学报 ,2008年21(04):22-24 ISSN：2095-5987
作者机构：
华中师范大学化学学院,武汉,430079;[杨光富; 张爱东; 涂海洋] 华中师范大学
关键词：
有机化学;研究型教学
摘要：
从教学内容的设计、教学策略的设计、教学方法的设计、辅导答疑、管理和成绩评定等几个方面介绍双语有机化学进行研究型教学的探索与实践,这种教学模式强调让学生自主地参与获得有机化学知识和技能,对学生创造性思维的培养起到很好的效果。
语种：
中文
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Bis(benzimidazole)pyridine derivative as a new class of G-quadruplex inducing and stabilizing ligand
作者：
Li, Guorui;Huang, Jing;Zhang, Ming;Zhou, Yangyang;Zhang, Dan;...
期刊：
Chemical Communications ,2008年(38):4564-4566 ISSN：1359-7345
通讯作者：
Zhou, Xiang
作者机构：
[Li, Guorui; Zhou, Yangyang; Huang, Jing; Zhou, Xiang; Zhang, Dan; Wu, Zhiguo; Zhang, Ming; Wang, Shaoru; Weng, Xiaocheng] Wuhan Univ, Coll Chem & Mol Sci, Minist Educ Res, Key Lab Biomed,State Key Lab Virol, Wuhan 430072, Peoples R China.;[Yang, Guangfu; Zhou, Xiang] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ Res, Coll Chem, Wuhan 430079, Peoples R China.
通讯机构：
[Zhou, Xiang] W;Wuhan Univ, Coll Chem & Mol Sci, Minist Educ Res, Key Lab Biomed,State Key Lab Virol, Wuhan 430072, Peoples R China.
摘要：
Two new bis(benzimidazole)aryl derivatives have been prepared and one of them has been shown to induce and stabilize formation of a G-quadruplex.
语种：
英文
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Binding interaction analysis of the active site and its inhibitors for neuraminidase (N1 subtype) of human influenza virus by the integration of molecular docking, FMO calculation and 3D-QSAR CoMFA modeling
作者：
Zhang, Qingye;Yang, Jiaoyan;Liang, Kun;Feng, Lingling
（ ;Li, Sanpin;...
期刊：
Journal of Chemical Information and Modeling ,2008年48(9):1802-1812 ISSN：1549-9596
通讯作者：
Wan, Jian
作者机构：
[Yang, Guangfu; Feng, Lingling; Li, Sanpin; Zhang, Qingye; Wan, Jian; Liang, Kun] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Xu, Xin] Xiamen Univ, Coll Chem & Chem Engn, Ctr Theoret Chem, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.;[Yang, Shao; Liu, Deli; Yang, Jiaoyan] Cent China Normal Univ, Coll Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Wan, Jian] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
Recently, the worldwide spread of A/H5N1 avian influenza with high virulence has highlighted the potential threat of human influenza pandemic. Tamiflu and Relenza are currently the only two anti-influenza drugs targeting the neuraminidase (NA) enzyme of human influenza virus. Reports of the emergence of drug resistance further make the development of new potent anti-influenza inhibitors a priority. The X-ray crystallographic study of A/H5N1 avian influenza NA subtypes (Russell, R. J. Nature 2006, 443, 45-49) has demonstrated that there exist two genetically distinct groups, group-1 (N1, N4, N5 and N8) andgroup-2 (N2, N3, N6, N7 and N9), whose conformations are substantially different The detailed comparison of their active sites has established, heretofore, the most accurate and solid molecular basis of structure and mechanism for the development of new anti-influenza drugs. In the present study, a rhree-dimensiooal structure of N1 subtype of human influenza type A virus (N1hA) has been generated by homology modeling using the X-ray crystallographic structure of Nl subtype of avian influenza virus (N1aA) as the template. Binding interaction analysis between the active site and its inhibitors has been performed by combining ab initio fragment molecular orbital (FMO) calculations and three-dimensional quantitative structure-activity relationship with comparative molecular field analysis (3D-QSAR CoMFA) modeling. Integrated with docking-based 3D-QSAR CoMFA modeling, molecular surface property (electrostatic and steric) mapping and FMO pair interaction analysis, a set of new receptor-ligand binding models and bioaffinity predictive models for rational design and virtual screening of more potent inhibitors of N1hA are established. In addition, the flexibility of the loop-150 of N1hA and N1aA has been examined by a series of molecular dynamics simulations. ©2008 American Chemical Society.
语种：
英文
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A capillary electrophoresis assay for recombinant Bacillus subtilis protoporphyrinogen oxidase
作者：
Ying Tan;Lu Sun;Zhen Xi;Guang-Fu Yang
（ ;Dong-Qing Jiang;...
期刊：
Analytical Biochemistry ,2008年383(2):200-204 ISSN：0003-2697
通讯作者：
Xi, Zhen
作者机构：
[Zhen Xi; Xing Yang; Lu Sun; Ying Tan; He-Yang Li] Nankai Univ, State Key Lab Element Organ Chem, Tianjin 300071, Peoples R China.;[Zhen Xi; Xing Yang; Lu Sun; Ying Tan; He-Yang Li] Nankai Univ, Dept Biol Chem, Tianjin 300071, Peoples R China.;[Guang-Fu Yang; Ying Tan] Cent China Normal Univ, Key Lab Pesticide & Chem Biol Minist Educat, Coll Chem, Wuhan 430079, Peoples R China.;[Dong-Qing Jiang; Xiu-Ping Yan] Nankai Univ, Res Ctr Analyt Sci, Coll Chem, Tianjin 300071, Peoples R China.
通讯机构：
[Xi, Zhen] N;Nankai Univ, State Key Lab Element Organ Chem, Tianjin 300071, Peoples R China.
关键词：
Capillary electrophoresis;FAD;Herbicide;Kinetics;Protoporphyrinogen oxidase
摘要：
Protoporphyrinogen oxidase (PPO) is a flavin adenine dinucleotide (FAD)-containing enzyme in the tetrapyrrole biosynthetic pathway that leads to the formation of both heme and chlorophylls, which has been identified as one of the most important action targets of commercial herbicides. The literature reports gave different PPO-catalytic kinetic parameters for the substrate protoporphyrinogen IX (Km of 0.1 to 10.4 μM) with different sources of PPO using fluorescent or HPLC methods. Herein we assayed the enzymatic activity of recombinant Bacillus subtilis PPO by using capillary electrophoresis (CE), a method with high separation efficiency, easy automation, and low sample consumption. The Michaelis constant and maximum reaction velocity were determined as 7.0 ± 0.6 μM and 0.38 ± 0.02 μmol min-1 μg-1, respectively. The interaction between PPO and acifluorfen, a commercial PPO-inhibiting herbicide, was measured as the inhibition constant 186.9 ± 9.3 μM{cyrillic}. The relationship between cofactor FAD and PPO activity can also be quantitatively studied by this CE method. The CE method used here should also be a convenient, reliable method for PPO study. © 2008 Elsevier Inc. All rights reserved.
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英文
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Synthesis, antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives
作者：
Chen, Qiong;Zhu, Xiao-Lei;Jiang, Li-Li;Liu, Zu-Ming;Yang, Guang-Fu
* （ 期刊：
European Journal of Medicinal Chemistry ,2008年43(3):595-603 ISSN：0223-5234
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Liu, Zu-Ming; Jiang, Li-Li; Chen, Qiong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
1,2,4-Triazolo[1,5-a]pyrimidine;1,3,4-Oxadiazole;Antifungal activity;CoMFA
摘要：
In order to search novel agrochemicals with higher antifungal activity, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives bearing 1,3,4-oxadiazole moieties were designed and synthesized. Their antifungal activities against Rhizoctonia solani were evaluated in vitro. By determining the EC50 values of all the newly synthesized compounds and 10 formerly synthesized compounds, compound 8r, 2-((5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)-methylthio)-5-dimethyl-1,2,4-triazolo-[1,5-a]pyrimidine, was found to display the highest antifungal activity (EC50 = 6.57 μg mL-1). Based on the quantitative structure-activity relationships analyses, 2-(1-(5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)ethylthio)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (9j) was designed and synthesized, which was found to display much higher activity (EC50 = 3.34 μg mL-1) than compound 8r and the control. To further explore the comprehensive structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed and a statistically reliable model with good predictive power (r2 = 0.929, q2 = 0.588) was achieved on the basis of the common substructure-based alignment. According to the CoMFA model, the structure-antifungal activity relationship was explained reasonably. © 2007 Elsevier Masson SAS. All rights reserved.
语种：
英文
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Synthesis and oxidation-induced DNA cross-linking capabilities of bis(catechol) quaternary ammonium derivatives
作者：
Song, Zhibin;Weng, Xiaocheng;Weng, Liwei;Huang, Jing;Wang, Xiaolin;...
期刊：
CHEMISTRY-A EUROPEAN JOURNAL ,2008年14(19):5751-5754 ISSN：0947-6539
通讯作者：
Zhou, Xiang
作者机构：
[Zhou, Yangyang; Weng, Liwei; Song, Zhibin; Huang, Jing; Wang, Xiaolin; Zhou, Xiang; Bai, Minghui; Weng, Xiaocheng] Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.;[Yang, Guangfu] Huazhong Normal Univ, Coll Chem, Wuhan 430072, Peoples R China.
通讯机构：
[Zhou, Xiang] W;Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China.
关键词：
catechol;DNA damage;enzymes;oxidation;quinones
摘要：
A study was conducted to demonstrate the synthesis of a number of DNA crosslinking agents, such as bis(catechol) quaternary ammonium derives. It was found that these agents can crosslink DNA through an o-quinone intermediate, induced by oxidation. It was also found that these compounds are composed of two catechol monomers, acting as DNA cross-linking units and are joined by different linkers that act as DNA binding units. Positive charged linkers and quaternary ammonium derivatives were used in the study, to achieve high affinity to DNA. Aliphatic and aromatic chains were investigated, to determine their ability in performing favorable cross-linking reactions and to determine the relationship between agent flexibility and DNA cross-linking abilities.
语种：
英文
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