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Research 2024年第1期2023卷 663-674页

作者： Yang Yu Zhe Wang Lingling Wang Qinghua Wang Rongfan Tang Sutong Xiang Qirui Deng Tingjun Hou huiyong sun Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 210009JiangsuP.R.China Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058ZhejiangP.R.China

Anaplastic lymphoma kinase(ALK),a tyrosine receptor kinase,has been proven to be associated with the occurrence of numerous *** there have been already at least 3 generations of ALK inhibitors approved by FDA or in clinical trials,the occurrence of various mutations seriously attenuates the effectiveness of the ***,most of the drug resistance mechanisms still remain ***,it is necessary to reveal the bottom reasons of the drug resistance mechanisms caused by the *** this work,on the basis of verifying the accuracy of 2 main kinds of binding free energy calculation methodologies[end-point method of Molecular Mechanics with Poisson-Boltzmann/Generalized Born and Surface Area(MM/PB(GB)SA)and alchemical method of Thermodynamic Integration(TI)],we performed a systematic analysis on the ALK systems to explore the underlying shared and specific drug resistance mechanisms,covering the one-drug-multiple-mutation and multiple-drug-onemutation cases.

关键词： drugs Anaplastic clinical

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia sun huiyong HAO Haiping ZHANG Bo XU Xiaowei State Key Laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Prediction of fibril formation by early-stage amyloid peptide aggregation

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Journal of Pharmaceutical Analysis 2020年第2期10卷 194-199页

作者： Jiaojiao Hu huiyong sun Haiping Hao Qiuling Zheng Department of Pharmaceutical Analysis School of PharmacyChina Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China Key Laboratoryof Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China

Amyloid fibrils are found in systemic amyloidosis diseases such as Alzheimer's disease,Parkinson's disease,and type II ***,these diseases are diagnosed by observation of fibrils or plaques,which is an ineffective method for early diagnosis and treatment of *** goal of this study was to develop a simple and quick method to predict the possibility and speed of fibril formation before its *** generated from seven representative peptide segments were first isolated and detected by ion-mobility mass spectrometry(IM-MS).Then,their assemblies were disrupted using formic acid(FA).Interestingly,oligomers that showed small ion intensity changes upon FA addition had rapid fibril *** contrast,oligomers that had large ion intensity changes generated fibrils *** control peptides(aggregation/no fibrils and no aggregation/no fibrils)did not show changes in their ion intensities,which confirmed the ability of this method to predict amyloid *** summary,the developed method correlated MS intensity ratio changes of peptide oligomers on FA addition with their amyloid *** method will be useful for monitoring peptide/protein aggregation behavior and essential for their mechanism studies.

关键词： Mass spectrometry Amyloid fibril Early-stage oligomer Peptide aggregation

2-Diphenylphosphinoyl-acetyl as a Remote Directing Group for the Highly Stereoselective Synthesis ofβ-Glycosides

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Chinese Journal of Chemistry 2022年第4期40卷 443-452页

作者： Xianglai Liu Yetong Lin Ao Liu Qianhui sun huiyong sun Peng Xu Guolong Li Yingying Song Weijia Xie Haopeng sun Biao Yu Wei Li Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical University639 Longmian AvenueNanjingJiangsu 211198China State Key Laboratory of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of Sciences345 Lingling RoadShanghai 200032China

Comprehensive Summary The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate ***,their stereochemistry control in glycosylation represe... 详细信息

关键词： Glycosylation Diastereoselectivity Hydrogen bonds 2-Diphenylphosphinoyl-acetyl 2-Deoxy sugars

氮-磷-铝阻燃剂的制备及其在皮革中的阻燃性能

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中国皮革 2024年第4期53卷 8-13,19页

作者：孙辉永刘琳温会涛林可心吴渝玉但卫华福建省皮革绿色设计与制造重点试验室福建晋江362271 中国轻工业制革绿色工程实验室福建晋江362271 兴业皮革科技股份有限公司国家企业技术中心福建晋江362261 四川大学制革清洁技术国家工程研究中心四川成都610065

采用分子设计方法制备了氮-磷-铝协同阻燃材料,并作为填料,通过阻燃赋性工艺引入皮胶原纤维之间,得到阻燃性能优良的阻燃功能皮革,并通过FTIR、^(1)H NMR、SEM、XPS、TG和DTG进行了表征。FTIR和^(1)H NMR表明已引入了目标结构,SEM、EDS... 详细信息

采用分子设计方法制备了氮-磷-铝协同阻燃材料,并作为填料,通过阻燃赋性工艺引入皮胶原纤维之间,得到阻燃性能优良的阻燃功能皮革,并通过FTIR、^(1)H NMR、SEM、XPS、TG和DTG进行了表征。FTIR和^(1)H NMR表明已引入了目标结构,SEM、EDS和XPS表明阻燃填料已引入到皮革的胶原纤维束之间;TG和DTG表明,阻燃填料的添加量越大,皮革的热分解温度越高,残留率也越大;阻燃测试结果表明,引入氮-磷-铝阻燃剂后,皮革具有较好的阻燃性,不燃烧,离开火焰后极易熄灭,不续燃;燃烧距离几乎为零,基本无质量损失,阻燃等级可达到UL 94 V-0,极限氧指数可达到354%。

关键词：制革工程阻燃性能氮-磷-铝填料功能皮革

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基于均匀设计的无铬复鞣工艺设计与优化

皮革与化工 2024年第1期41卷 9-14页

作者：孙辉永林可心温会涛刘琳吴渝玉但卫华福建省皮革绿色设计与制造重点试验室福建晋江362271 中国轻工业制革绿色工程实验室福建晋江362271 兴业皮革科技股份有限公司国家企业技术中心福建晋江362261 四川大学制革清洁技术国家工程研究中心四川成都610065

为提高皮革复鞣工艺的生态性能,以锆-铝-钛鞣白湿革为原料皮,以皮革的热收缩温度、撕裂强度、感官性能和复鞣排放废液中的COD含量作为评价指标,设计并优化基于改性戊二醛、锆铝钛配合鞣剂和阳离子油的无铬复鞣工艺。结果表明,当改性戊... 详细信息

为提高皮革复鞣工艺的生态性能,以锆-铝-钛鞣白湿革为原料皮,以皮革的热收缩温度、撕裂强度、感官性能和复鞣排放废液中的COD含量作为评价指标,设计并优化基于改性戊二醛、锆铝钛配合鞣剂和阳离子油的无铬复鞣工艺。结果表明,当改性戊二醛鞣剂用量为2%、锆-铝-钛配合鞣剂用量为2%、阳离子油用量为0.4%时,复鞣效果和生态性能好,复鞣后的坯革也具有较好的耐热性能、感官性能和物理性能。这为皮革的生态设计提供了一种新思路。

关键词：制革工程无铬复鞣均匀设计生态皮革生态设计

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Discovery of Novel Androgen Receptor Ligands by Structure-based Virtual Screening and Bioassays

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Genomics, Proteomics & Bioinformatics 2018年第6期16卷 416-427页

作者： Wenfang Zhou Mojie Duan Weitao Fu Jinping Pang Qin Tang huiyong sun Lei Xu Shan Chang Dan Li Tingjun Hou College of Pharmaceutical Sciences Zhejiang University State Key Laboratory of Computer Aided Design and Computer Graphics (CAD&GC) Zhejiang University State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsChinese Academy of Sciences Institute of Bioinformatics and Medical Engineering School of Electrical and Information EngineeringJiangsu University of Technology

Androgen receptor(AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling ***, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening(VS) on the basis of the crystal structure of the AR ligand binding domain(LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them(HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC50 values of HBP1-51 and HBP1-58 are 3.96 m M and 4.92 m M, respectively, which are even lower than that of enzalutamide(Enz, IC50= 13.87 m M), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics(MD) simulations and principal components analysis(PCA) were carried out to reveal the binding principle of the newlyidentified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary,the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases.

关键词： Androgen receptor AR ligand Virtual screening AR agonist AR antagonist

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国产准移动信号系统在长春轻轨的应用研究

都市快轨交通 2012年第6期25卷 8-11页

作者：孙会勇长春市轨道交通集团有限公司长春130012

对国产FZL型信号系统在长春轻轨3号线的实际应用进行阐述。介绍该系统的特点及在3号线的配置情况,分析3号线一、二期混跑的运营模式以及贯通后的运营模式。实际应用的效果表明,该系统具有造价低、可靠性高、适应性广等优点,能满足特殊... 详细信息

对国产FZL型信号系统在长春轻轨3号线的实际应用进行阐述。介绍该系统的特点及在3号线的配置情况,分析3号线一、二期混跑的运营模式以及贯通后的运营模式。实际应用的效果表明,该系统具有造价低、可靠性高、适应性广等优点,能满足特殊运营模式的要求,可作为中小运量轨道交通线路信号系统制式的一个选择。

关键词：长春轻轨信号系统准移动闭塞轨道电路超速防护

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蛹虫草对锌的耐性与富集特征

生态学报 2010年第6期30卷 1449-1455页

作者：程显好盖宇鹏孙慧涌柏新富张秋胜鲁东大学生命科学学院烟台264025

在培养基内添加不同量的锌,研究其对蛹虫草子实体的形成、子实体和菌丝体生物量、子实体多糖含量和葡萄糖含量的影响,以及蛹虫草子实体和菌丝体对锌的富集能力。结果表明锌对上述各项都有影响。液体培养条件下,锌浓度在453906mg/L范围... 详细信息

在培养基内添加不同量的锌,研究其对蛹虫草子实体的形成、子实体和菌丝体生物量、子实体多糖含量和葡萄糖含量的影响,以及蛹虫草子实体和菌丝体对锌的富集能力。结果表明锌对上述各项都有影响。液体培养条件下,锌浓度在453906mg/L范围内可以促进菌丝体生长,锌浓度超过4077mg/L时,菌丝生长受到抑制。培养基锌的浓度在4077mg/L以下时,蛹虫草菌丝体锌的富集量随着液体培养基锌浓度的提高而提高。固体培养条件下,锌含量在226453mg/kg范围内可以促进蛹虫草子实体生长,并且在此含量范围内,蛹虫草子实体中葡萄糖含量较高。培养基锌含量在680906mg/kg时,子实体多糖含量较高。培养基锌含量在2038mg/kg以下时,蛹虫草子实体中锌的富集量随着培养基锌含量的提高而提高,在培养基锌含量为2038mg/kg时,子实体中锌的含量达到28570mg/kg(干重)。

关键词：子实体菌丝体锌超积累

嘧啶类抑制剂与CDK2和CDK9选择性结合机理的理论研究

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嘧啶类抑制剂与CDK2和CDK9选择性结合机理的理论研究