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Identification and Characterization of glnA Promoter and its Corresponding Trans-regulatory Protein GlnR in the Rifamycin SV Producing Actinomycete,Amycolatopsis mediterranei U3.

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Acta Biochimica et Biophysica Sinica 2006年第12期38卷 831-843页

作者： Hao YU~(1&) Wen-Tao PENG~1 Yang LIU~1 Ting WU~2 Yu-Feng YAO~1 Ming-Xue CUI~1 Wei-Hong JIANG~1 Guo-Ping ZHAO~(1,3.4*) 1 Laboratory of Molecular Microbiology,Institute of Plant Physiology and Ecology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 20003.,china 2 department of medicinal chemistry,{3.,fudan university,Shanghai 20003.,china 3.State Key Laboratory of Genetic Engineering & department of Microbiology,school of Life Science,fudan university,Shanghai 20043.,china 4 Laboratory of Disease and Health Genomics,Chinese National Human Genome Center at Shanghai,Shanghai 201203.china Laboratory of Molecular Microbiology Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China department of medicinal chemistry School of Pharmacy Fudan University Shanghai 200032 China State Key Laboratory of Genetic Engineering & department of Microbiology School of Life Science Fudan University Shanghai 200433 China Laboratory of Disease and Health Genomics Chinese National Human Genome Center at Shanghai Shanghai 201203 China

The genetic requirements for the transcription of glnA,encoding the major glutaminesynthetase in a rifamycin SV-producing Amycolatopsis mediterranei strain,U3.,were *** experiments showed that the promoter of U3. glnA （pglnA） was likely to have two transcriptioninitiation sites:P1and P2,located 157 and 45 nucleotides （nt） upstream of the translational start codon,*** mobility shift and DNase I footprinting analyses revealed a 3. bp cis-element locatedat 45 to 75 nt downstream of P1,or 3. to 68 nt upstream of *** sequence of the cis-element displayedhigh similarity to the corresponding regions of pglnA from Streptomyces coelicolor and *** as a reporter gene,the expression levels of U3. pglnA and its deletion derivatives under differentnitrogen-source conditions were analyzed by detecting the catechol dioxygenase activities in ***54,*** J508 and *** FS10 （glnR mutant）.These in vivo studies showed that theactivation of U3. pglnA in *** required GlnR,and its binding to the U3. pglnA was furtherconfirmed by the gel mobility shift *** and heterologous expression of the U3. glnR allowed usto detect the in vitro interaction between the U3. GlnR and the corresponding pglnA *** shown by in vivo glnR inactivation and complementation indicated that GlnR is essential for theactive transcription of glnA in U3..

关键词： glnA promoter cis-element glnR Amycolatopsis mediterranei

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Role of Apolipoprotein A-I in Protecting against Endotoxin Toxicity

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 419-424页

作者： Juan MA, Xue-Ling LIAO, Bin LOU, and Man-Ping WU* department of Biochemistry, school of pharmacy, {3., Shanghai 20003., china department of Biochemistry School of Pharmacy Fudan UniversityShanghai 200032 China

High density lipoprotein (HDL) binds lipopolysaccharide (LPS or endotoxin) and neutralizes its toxicity. We investigated the function of Apolipoprotein A-I (ApoA-I), a major apolipoprotein in HDL, in this process. Mouse macrophages were incubated with LPS, LPS+ApoA-I, LPS+ApoA-I+LFF (lipoprotein-free plasma fraction d>1.210 g/ml), LPS+HDL, LPS+HDL+LFF, respectively. MTT method was used to detect the mortality of L-929 cells which were attacked by the release-out cytokines in LPS-activated macrophages. It was found that ApoA-I significantly decreased L-929 cells mortality caused by LPS treatment (LPS vs. LPS+ApoA-I, P20%) and in LPS+ApoA-I+LFF group (10%) was signifi- cantly lower than that in LPS group (80%) (P3.20 ± 10.13. h in LPS+ApoA-I group and (46.80 ± 3.79) h in LPS+ApoA-I+LFF group, which were significantly longer than that in LPS group (16.25 ± 17.28) h (P24.3. ± 3.70) (P2) LFF enhances the effect of ApoA-I; (3. ApoA-I is the major contributor for HDL anti-endotoxin function.

关键词： Apolipoprotein-I lipopolysaccharide (LPS) macrophages FITC-lipopolysaccharide (FITC-LPS) L-929 cells

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Diterpenoid Alkaloids from Aconitum racemulosum Franch var. pengzhouense

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Chinese Chemical Letters 2000年第5期11卷 411-414页

作者： Chong Sheng PENG Xi Xian JIAN Feng Peng WANG Dong Lin CHEN (department of chemistry of medicinal Natural Products, {3., West china university of Medical Sciences, Chcngdu 610041) W china Univ Med Sci Sch Pharm Dept Chem Med Nat Prod Chengdu 610041 Peoples R China

A new diterpenoid alkaloid, racemulodine (1), was isolated from the whole plants of Aconitum racemulosum Franch var. pengzhounense.

关键词： Aconitum racemulosum Franch var. pengzhounense Ranunculaceae racemulodine

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Distribution of nimodipine in brain following intranasal administration in rats

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Acta Pharmacologica Sinica 2004年第4期25卷 124-129页

作者： Qi-zhi ZHANG, Xin-guo JIANG2, Chun-hua WU department of Pharmaceutics, school ofpharmacy, {3., Shanghai 20003., china department of Pharmaceutics School of Pharmacy Fudan University

AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed byHPLC. RESULTS: Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 3. min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.3. fold compared with the iv route, respectively. The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

关键词： intranasal administration nimodipine olfactory bulb olfactory pathways

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Bacterial Type Ⅰ Glutamine Synthetase of the Rifamycin SV Producing Actinomycete,Amycolatopsis mediterranei U3.,is the Only Enzyme Responsible for Glutamine Synthesis under Physiological Conditions

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Acta Biochimica et Biophysica Sinica 2006年第12期 821-830页

作者： Wen-Tao PENG~(1&) Jin WANG~1 Ting WU~2 Jian-Qiang HUANG~1 Jui-Shen CHIAO~1 Guo-Ping ZHAO~(1,3.4) 1 Laboratory of Molecular Microbiology,Institute of Plant Physiology and Ecology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 20003.,china 2 department of medicinal chemistry,{3.,fudan university,Shanghai 20003.,china 3.State Key Laboratory of Genetic Engineering/department of Microbiology,school of Life Science,fudan university,Shanghai 20043.,china 4 Laboratory of Health and Disease Genomics,Chinese National Haman Genome Center at Shanghai,Shanghai 201203.china

The structural gene for glutamine synthetase,glnA,from Amycolatopsis mediterranei U3. wascloned via screening a genomic library using the analog gene from Streptomyces *** clone wasfunctionally verified by complementing for glutamine requirement of an Escherichia coli glnA null mutantunder the control of a lac *** analysis showed an open reading frame encoding a protein of466 amino acid *** deduced amino acid sequence bears significant homologies to other bacterialtype Ⅰ glutamine synthetases,specifically,71% and 72% identical to the enzymes of *** and Myco-bacterium tuberculosis,*** of this glnA gene in *** U3. led to glutamineauxotrophy with no detectable glutamine synthetase activity in *** contrast,the cloned glnA+gene cancomplement for both phenotypes in *** thus suggested that in *** U3.,the glnA geneencoding glutamine synthetase is uniquely responsible for in vivo glutamine synthesis under our laboratorydefined physiological conditions.

关键词： glnA glutamine synthetase Amycolatopsis mediterranei rifamycin SV

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Conformational re-analysis of(+)-meptazinol:an opioid with mixed anal-gesic pharmacophores

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Acta Pharmacologica Sinica 2006年第9期27卷 1247-1252页

作者： Wei LI~2 Xing-hai WANG~2 Choi-wan LAU~3.Yun TANG~(2,4)Qiong XIE~2 Zhui-bai QIU~(2,5)2 department of medicinal chemistry 3.NMR Laboratory,school of pharmacy,fudan university,Shanghai {3.,china 4 school of pharmacy,East china university of Science and Technology,Shanghai 20023.,china departmentofmedicinalchemistry NMRLaboratory SchoolofPharmacyFudanUniversityShanghai200032China schoolofpharmacy EastChinaUniversityofScienceandTechnologyShanghai200237China

Aim:To further investigate the analgesic pharmacophore of(+)-***:Two different opioid pharmacophores,Pharm-Ⅰ and Pharm-Ⅱ,were es-tablished from structures of nine typical opiates and meperidine by using molecu-lar modeling approaches according to their different structure activity relation-ship *** were further validated by a set of conformationally con-strained *** conformers of(+)-meptazinol(Conformer-Ⅰ and Con-former-Ⅱ)detected in solution were then fitted into the pharmacophores,respectively,by Fit Atoms facilities available in SYBYL,a computational modelingtool kit for molecular design and ***:Conformer-Ⅰ fit Pharm-Ⅰ fromtypical opiates ***,Conformer-Ⅱ fit none of these ***,it was found to be similar to another potent analgesic,benzofuro[2,3.c]pyridin-6-ol,whose pharmacophore was suggested to hold the transitional statebetween the two established *** typical analgesics derivedfrom 4-aryl piperidine(eg,meperidine)with one conformer absolutely overwhelming,the(+)-meptazinol exists in two conformers with similar amounts in ***,both conformers can not transform to each other freely in ordinaryconditions based on our NMR ***:(+)-meptazinol was suggestedto be an opioid with mixed analgesic pharmacophores,which may account for thecomplicated pharmacological properties of meptazinol.

关键词： (+)meptazinol opioid analgesics arylpiperidines Conformational Analysis,pharmacophore.

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Structural comparisons of meptazinol with opioid analgesics

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Acta Pharmacologica Sinica 2005年第3期26卷 334-338页

作者： Wei LI Jing-lai HAO Yun TANG Yan CHEN Zhui-bai QIU~2 department of medicinal chemistry,school of pharmacy,fudan university Shanghai {3.,china departmentofmedicinalchemistry SchoolofPharmacyFudanUniversityShanghai200032China

Aim:To investigate the mechanism of action of a potent analgesic,(±)-***:The structures of meptazinol enantiomers were compared with opioidpharmacophore and ***:Neither enantiomer of meptazinol fittedany patterns among the opioid pharmacophore and tramadol,although they didshare some structural and pharmacological ***,the structuresuperpositions implied that both enantiomers of meptazinol might share somesimilar analgesic mechanisms with typical opiate ***:Meptazinol should have a different mechanism of action to known analgesics,which would be helpful in further investigations of meptazinol in the search fornon-addictive analgesics.

关键词： meptazinol tramadol opioid analgesics pharmacophore

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Two new C_(19)-diterpenoid alkaloids from roots Aconitum hemsleyanium var. atropurpureum

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Chinese Chemical Letters 2007年第6期18卷 704-707页

作者： Pei Tang, Dong Lin Chen, Xi Xian Jian, Feng Peng Wang department of chemistry of medicinal Natural Products, West {3. College of pharmacy, Sichuan university, Chengdu 610041, {3. [a]department of chemistry of medicinal Natural Products West China College of Pharmacy Sichuan University Chengdu 610041 China

A new franchetine-type C19-diterpenoid alkaloid 3.hydroxyfranchetine 1 and a new aconitine-type C19-diterpenoid alkaloid atropurpursine 2 have been isolated from the roots of Aconitum hemsleyanium var. atropurpureum. ... 详细信息

关键词： Aconitum hemsleyanium var. atropurpureum Rranunculaceae C19-diterpenoid alkaloid 3.Hydroxyfranchetine Atropurpursine

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Organocatalytic asymmetric allylic alkylation of sulfonylimidates with Morita-Baylis-Hillman carbonates

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Science china chemistry 2011年第1期54卷 81-86页

作者： PENG Jing,CUI HaiLei & CHEN YingChun Key Laboratory of Drug-Targeting and Drug Delivery System,Ministry of Education department of medicinal chemistry,West {3. school of pharmacy,Sichuan university,Chengdu 610041,{3. 1. Key Laboratory of Drug-Targeting and Drug Delivery System Ministry of Education department of medicinal chemistry West China School of Pharmacy Sichuan University Chengdu 610041 China

The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was accomplished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)*** corresponding allylic alkylation products were obtained in good yields with high stereoselectivities (up to 99% ee,89:11 dr).

关键词： organocatalysis asymmetric allylic alkylation sulfonylimidates Morita-Baylis-Hillman carbonates cinchona alkaloids

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Risk factors of adverse drug reaction from non-steroidal anti-inflammatory drugs in Shanghai patients with arthropathy

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Acta Pharmacologica Sinica 2004年第3期25卷 103-111页

作者： Wen SHI2,Yong-ming WANG,Shao-li LI3.Min YAN3.Duan Li,Bin-yan CHEN,Neng-neng CHENG department of Pharmacology,school of pharmacy,fudan university,Shanghai {3. The Center for Drug Reevaluation and 3.The Center for Adverse Drug Reaction Monitoring,State Food and Drug Administration,Beijing 100061,china department of Pharmacology School of Pharmacy Fudan University The Center for Drug Reevaluation and The Center for Adverse Drug Reaction Monitoring State Food and Drug Administration Beijing 100061 China

AIM: The study was to screen the possible risk factors of adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Shanghai patients with arthropathy. METHODS: The subjects were ran- domly selected from a database of outpatients with arthropathy from 9 main hospitals in Shanghai. A door to door retrospective epidemiological survey was used to collect demographic information about the patients, both indi- vidual and familial. This included data on their medical histories, lifestyle and dietary habits, history of smoking and alcohol consumption, history of drug therapy, quality of life (QOL) prior to NSAIDs intake, history of NSAIDs therapy and its ADR events, etc. Descriptive statistical methods and univariate analysis were also used to identify possible risk factors for ADRs induced by NSAIDs. RESULTS: Of the 1002 patients surveyed, the average length of NSAIDs intake was 2 years. ADR incidence from different NSAIDs was high, in a range from 46.7 %-66.2 %. In general, the candidate risk factors for ADRs were different for each NSAID. Each of the candidate risk factors were defined and studied in order to evaluate its role in the determination of ADRs from NSAIDs. “Family history of ADRs caused by NSAIDs” was found to be a significant risk factor for the four commonly used NSAIDs: meloxicam, diclofenac, nimesulide, and nabumetone. CONCLUSION: A retrospective epidemiological survey was useful in detecting the risk factors for ADRs caused by NSAIDs. The study found that different NSAIDs might have different risk factors and that there is no single risk factor universally applicable to all NSAIDs.

关键词： non-steroidal anti-inflammatory drugs adverse drug reaction risk factors retrospective studies quality of life

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