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Two Concise Methods to Prepare Peptide-oligonucleotide Conjugates

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Two Concise Methods to Prepare Peptide-oligonucleotide Conju...

第五届全国化学生物学学术会议

作者： Fei-lin Nie zhen-jun yang~* liang-ren zhang li-he zhang state key laboratory of natural and biomimetic drugs,school of pharmaceutical sciences,peking university,beijing100083

＜正＞RNA interference（RNAi）has been rapid progress towards its application as one of the most important molecular in molecular *** order to enhance siRNA’s stability,cell uptaken and gene silence effect,we designe... 详细信息

关键词： RNA interference peptide-oligonucleotide conjugates

Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-6-one:Methyl Shift of 4-Methoxy-5-chloropyridazin-6-one

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Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-...

第三届全国有机化学学术会议

作者： liN, Gui-Chun yang, zhen-jun zhang, liang-ren liU, li zhang, li-he ( The state key laboratory of natural and biomimetic drugs , school of pharmaceutical sciences , peking university health science Center, beijing 100083)

＜正＞ N1-Trifluoroethyl-4-methoxy-5-chloro-3-pyridazone （4） was synthesized by the substitution reaction of 4 methoxy-5-chloro-3-pyridazone （1） with trifluoroethyl trifluoromethanesulfonate （A） at basic condition. In the most of reaction conditions,N1-methyl-4-methoxy-5-chloro-3-pyridazone （2） was obtained as a major by-product, which means that the methyl group in the 4-methoxy shifted to N-1 position inter-molecularly aided by A or trifluoroethyl methanesulfonate （B） . We obtained N1-methyl-4-trifluoro-ethoxy-5-chloro-3-pyridazone （3） in the reaction of 1 with

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Design,Synthesis,and Biological Evaluation of Trifluoromethylated Cyclic-ADP-Ribose Mimics:8-trifluoromethyl-N1-[(5”-O-Phosphorylethoxy)methyl]-5'-O-phosphorylino sine 5',5”-Cyclic pyrophosphate(8-CF3-cIDPRE)and 8-CF3-2',3'-O-isopropylidene cIDPRE

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Design,Synthesis,and Biological Evaluation of Trifluoromethy...

第六届全国化学生物学学术会议

作者： Min Dong,Xiang-Cheng Huang.zhen-jun yang,~* liang-ren zhang,li-he zhang~* state key laboratory of natural and biomimetic drugs,school of pharmaceutical sciences peking university.beijing.100191.

Cyclic ADP-ribose(cADPR) was discovered as a Ca mobilizing metabolite ofβ-nicotinamide adenine dinucleotide(NAD) by Lee and *** inositol 1,4,5-trisphosphate(InsP3) and nicotinic acid adenine dinucleotide phosphate(NA...

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A novel method for the synthesis of sulfur substituted-cyclopyrophosphate of cADPR analogs

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Chinese Chemical Letters 2014年第12期25卷 1583-1585页

作者： ren-Min Wu Na Qi Yu-Wen Jia Zhu Guan liang-ren zhang li-he zhang zhen-jun yang state key laboratory of natural and biomimetic drugs School of Pharmaceutical SciencesPeking University

A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was *** key step was the cyclization process which was completed by the sulfur substituted cyclizati... 详细信息

关键词： cADPR cIDPRE Phosphoramidite strategy Cyclopyrophosphate

Synthesis,physicochemical and biological properties of oligonucleotides incorporated with amino-isonucleosides

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science China Chemistry 2012年第1期55卷 70-79页

作者： WANG Fang CheN Yue HUANG Ye JIN Hong-Wei zhang liang-ren yang zhen-jun zhang li-he state key laboratory of natural and biomimetic drugs school of pharmaceutical sciences Peking UniversityBeijing 100191China

Antisense oligonucleotides(ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression,and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral *** order to improve bioactivity properties and physicochemical properties of siRNA,we synthesized a novel class of ASONs II-VII incorporated with amino-isonucleoside(isoA1 and isoA2) for investigation on basic physicochemical *** we designed amino-isonucleoside(isoA1,isoA2 and isoT1) incorporated siRNA *** meaningful results have been obtained from the physicochemical property experiments in *** RNAi potency experiments,we investigated RNAi potency of each strand of the *** amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position *** off target effect from sense strand loading in siRNA application was observed.

关键词： amino-isonucleoside antisense oligonucleotide siRNA

Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-6-one: Methyl Shift of 4-Methoxy-5-chloropyridazin-6-one

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有机化学 2003年第Z1期23卷 30-31页

作者： liN Gui-Chun yang zhen-jun zhang liang-ren liU li zhang li-he The state key laboratory of natural and biomimetic drugs School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100083 The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100083 The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100083 The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100083 The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100083

　　N1-Trifluoroethyl-4-methoxy-5-chloro-3-pyridazone (4) was synthesized by the substitution reaction of 4methoxy-5-chloro-3-pyridazone (1) with trifluoroethyl trifluoromethanesulfonate (A) at basic condition. In the most of reaction conditions, N1-methyl-4-methoxy-5-chloro-3-pyridazone (2) was obtained as a major by-product, which means that the methyl group in the 4-methoxy shifted to N-1 position inter-molecularly aided by A or trifluoroethyl methanesulfonate (B). We obtained N1-methyl-4-trifluoro-ethoxy-5-chloro-3-pyridazone (3) in the reaction of 1 with B at higher temperature in different solvents with different yield (Table 1 ), which mechanism was shown in Figure 1. When we tried to synthesize 4 in the reaction of 1 with trifluoroethyl toluenesulfonate under basic condition, 6 was obtained (Figure 2). All the detailed mechanisms are undergoing investigated.……

关键词： substitution reaction higher temperature

Synthesis,physicochemical and biological properties of oligonucleotides incorporated with amino-isonucleosides

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中国科学：化学 2012年第2期42卷 213-214页

作者： WANG Fang CheN Yue HUANG Ye JIN Hong-Wei zhang liang-ren yang zhen-jun zhang li-he state key laboratory of natural and biomimetic drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

关键词：反义寡核苷酸异核苷氨基酸生物学特性注册合成 siRNAs 抗病毒治疗

CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen Huirun Chen Jinhui Chen Ji-Yuan Chen Kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH university of science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui university HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu university Institute of ScienceVaranasi Bandirma Onyedi Eylul university Bandirma Beihang university Beijing beijing Computational science Research Center Beijing beijing Conveyi LTD Beijing beijing Glass Research Institute Co. LtdBeijing beijing Institute of Technology Beijing beijing Normal university Beijing Brown university ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad university Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo university Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal university WuhanHubei Central South university ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu KaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang university HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China university of Geosciences Beijing China university of Geosciences WuhanHubei China university of Mining and Technology XuzhouJiangsu China West Normal university NanchongSichuan Chongqing university Department of PhysicsChongqing Chulalongkorn university Bangkok City university of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell university IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu university DalianLiaoning Dalian university of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East China university Of science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

Insight into the deamination mechanism of 6-cyclopropylamino guanosine analogs for anti-HIV drug design

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Chinese Chemical Letters 2016年第12期27卷 1759-1762页

作者： Xin-Meng Fan Xian-Tao yang Yu-Jia Guo ren-Min Wu De-lin Pan Zhu Guan Xiao-Mei ling li-he zhang zhen-jun yang state key laboratory of natural and biomimetic drugs School of Pharmaceutical Sciences Peking University

Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis （CE） without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase （ADA）. A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly, D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-Kuanosine analogs for the treatment of HIV,

关键词： Deamination 6-Cyclopropylamino guanosine Mouse liver homogenate Adenosine deaminase Anti-HIV drug design