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Natural products,PGC-1α,and Duchenne muscular dystrophy

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Acta Pharmaceutica Sinica B 2020年第5期10卷 734-745页

作者： Ipek Suntar[ Antoni Sureda Tarun Belwal Ana Sanches Silva Rosa Anna Vacca Devesh Tewari Eduardo Sobarzo-Sánchez Seyed Fazel Nabavi Samira Shirooie Ahmad Reza Dehpour Suowen Xu Bahman Yousefi Maryam Majidinia Maria Daglia Giuseppe D’Antona Seyed Mohammad Nabavi department of Pharmacognosy Faculty of PharmacyGazi UniversityEtilerAnkara 06330Turkey Research Group in Community Nutrition and Oxidative Stress Health Research Institute of the Balearic Islands(IdISBa)and CIBEROBN(Physiopathology of Obesity and Nutrition)University of Balearic IslandsPalmaBalearic Islands E-07122Spain G.B.Pant National Institute of Himalayan Environment and Sustainable Development AlmoraUttarakhand 263643India National Institute for Agricultural and Veterinary Research(INIAV) VairaoVila do CondePortugal Center for Study in Animal Science(CECA) ICETAUniversity of PortoPortoPortugal Institute of Biomembranes Bioenergetics and Molecular BiotechnologiesNational Council of ResearchBari 70126Italy department of Pharmacognosy School of Pharmaceutical SciencesLovely Professional UniversityPhagwaraPunjab 144411India Laboratory of Pharmaceutical chemistry Faculty of PharmacyUniversity of Santiago de CompostelaSantiagode Compostela 15782Spain department of Organic chemistry Faculty of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Applied Biotechnology Research Center Baqiyatallah University of Medical SciencesTehran ***Iran Pharmaceutical Sciences Research Center Health InstituteKermanshah University of Medical SciencesKermanshah ***Iran department of pharmacology Faculty of MedicineTehran University of Medical SciencesTehran ***Iran Experimental Medicine Research Center Tehran University of Medical SciencesTehran ***Iran The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China molecular Medicine Research Center Tabriz University of Medical SciencesTabriz 516615731Iran Drug Applied Research Center Tabriz University of Medical SciencesTabriz 516615731Iran Solid Tumor Research Center Urmia University of Medical SciencesUrmia 571478334Iran department of Pharmacy University of Naples FedericoⅡNaples 80138Italy International Research Center for Foo

Peroxisome proliferator-activated receptorγ(PPARγ)is a transcriptional coactivator that binds to a diverse range of transcription ***γcoactivator 1(PGC-1)coactivators possess an extensive range of biological effects in different tissues,and play a key part in the regulation of the oxidative metabolism,consequently modulating the production of reactive oxygen species,autophagy,and mitochondrial *** to these findings,a large body of studies,aiming to establish the role of PGC-1 in the neuromuscular system,has shown that PGC-1 could be a promising target for therapies targeting neuromuscular *** these,some evidence has shown that various signaling pathways linked to PGC-1αare deregulated in muscular dystrophy,leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species(ROS)*** the light of these results,any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular ***-1αis influenced by different patho-physiological/pharmacological *** products have been reported to display modulatory effects on PPARγactivation with fewer side effects in comparison to synthetic *** together,this review summarizes the current knowledge on Duchenne muscular dystrophy,focusing on the potential effects of natural compounds,acting as regulators of PGC-1α.

关键词： Muscular dystrophy Natural product Peroxisome proliferator-activated receptor Y coactivator la PPARγactivation Reactive oxygen species Mitochondrial oxidative phosphorylation

季铵盐类相转移催化剂的介绍与其在异相亲核取代反应中的应用——介绍一个国外本科生实验并讨论其相关问题

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化学教育（中英文） 2019年第16期40卷 89-93页

作者：马新雨王志鹏许兵王鹏缑允梓颜惠娟蒋振雄 department of chemistry Texas A&M UniversityCollege StationTX77840USA Division of Genetics Department of MedicineBrigham and Women’s Hospital department of biological chemistry andmolecular pharmacology Harvard Medical SchoolBostonMA02115USA Plant Pathology&Microbiology department.Texas A&M University Texas77840USA 中山大学附属第一医院烧伤外科广东广州510080 department of Biology Texas A&M UniversityCollege StationTX77840USA

介绍了一个国外大学化学专业本科生有机化学实验'相转移催化剂的应用',介绍了实验设计与流程,分析了实验结果,并讨论其相关的问题。该实验涉及到整套的现代有机合成流程,如薄层层析色谱(TLC)技术与硅胶柱色谱分离技术,并通过半微量反应... 详细信息

介绍了一个国外大学化学专业本科生有机化学实验'相转移催化剂的应用',介绍了实验设计与流程,分析了实验结果,并讨论其相关的问题。该实验涉及到整套的现代有机合成流程,如薄层层析色谱(TLC)技术与硅胶柱色谱分离技术,并通过半微量反应的设计,减少对环境有害物质的使用,体现了'绿色化学'的设计理念,值得国内本科生有机化学实验借鉴与学习。

关键词：本科生实验相转移催化剂亲核取代反应薄层层析色谱

生物化学中酶促“不可逆”反应及其相关问题辨析

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大学化学 2019年第4期34卷 77-83页

作者：马新雨王志鹏田杰蒋振雄姜汉杰孙鹤周青璇王鑫 department of chemistry Texas A&M University College Station Division of Genetics Department of Medicine Brigham and Women’s Hospital department of biological chemistry and molecular pharmacology Harvard Medical School department of Biology Texas A&M University College Station 南方科技大学化学系广东深圳518055 Broad Institute of MIT and Harvard Cambridge department of Medicine Harvard Medical School Renal Division Brigham and Women’s Hospital department of Microbiology Miami University

在生物化学教学和研究中,一些酶促反应被归类为不可逆反应。然而,此处的"不可逆"与物理化学中的"不可逆"有所不同,这一表述本身常导致学生的困惑。不仅如此,"不可逆"的实际含义及其衍生的观念可能进一步使学生产生很多对基本生化反应过... 详细信息

在生物化学教学和研究中,一些酶促反应被归类为不可逆反应。然而,此处的"不可逆"与物理化学中的"不可逆"有所不同,这一表述本身常导致学生的困惑。不仅如此,"不可逆"的实际含义及其衍生的观念可能进一步使学生产生很多对基本生化反应过程的严重误解。本文以物理化学所定义的"不可逆"为准,重新讨论生物化学中所指"不可逆"的准确含义,并举例讨论了包括"速控步""限速酶""高能磷酸键"在内的若干因生物化学中"不可逆"的不准确定义造成的认知误区。

关键词：酶促反应可逆反应化学平衡

Self-Assembled Binuclear Cu(Ⅱ)-L-Histidine Complex in the Gas Phase for Chiral Differentiation of Naproxen

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Self-Assembled Binuclear Cu(Ⅱ)-L-Histidine Complex in the G...

Computational pharmacology Study of Tougu Xiaotong Granule(透骨消痛颗粒) in Preventing and Treating Knee Osteoarthritis

2018年中国质谱学术大会（CMSC2018）

作者： Xiangying Yu Man-Chu Chau Wai Kit Tang Chi-Kit (Andy) Siu Zhong-Ping Yao State Key Laboratory of Chinese Medicine and molecular pharmacology (Incubation) and Shenzhen Key Laboratory of Food biological Safety Control Shenzhen Research Institute of Hong Kong Polytechnic University School of Chemical Engineering and Energy Technology Dongguan University of Technology department of chemistry City University of Hong Kong State Key Laboratory of Chirosciences Food Safety and Technology Research Centre and Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic University Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules (Yanbian University) Ministry of Education

Naproxen is one of the most consumed nonsteroidal anti-inflammatory drugs and marketed as Snaproxen as its R-enantiomer is hepatotoxic [1]. Developments of efficient and reliable methods for chiral differentiation and quantification of naproxen are thus essential [2]. In this work [3], we discovered a self-assembled binuclear Cu(II) diastereomeric complex ion in the gas phase, [(Cu IIL-His)2(S/R-naproxen)-3 H]+, that can be applied to effectively determine the absolute configuration of naproxen and quantify the enantiomeric excess of S/R-naproxen mixtures using collision-induced dissociation with a tandem mass spectrometer. The key candidate structure of this gas-phase diastereomeric complex ion has an unusual self-assembled, compact geometry with the two Cu(II) ions bridged closely together by the carboxylate groups of the two histidines, proposed using density functional theory, and supported by ion-mobility spectrometry and collision cross section modeling. The difference in dissociation efficiency of the two diastereomers is attributed to the σ-π interaction between the NH2 group of one histidine and the naphthyl ring of naproxen in the complex. The present report observes and characterizes the diastereomeric complexes of [(Cu IIL-His)2] with aromatic acid, which could contribute to the recognition of chiral aromatic acids, design of catalysts based on binuclear copper-bound complex, as well as the better understanding of metal-ion complexation by His or His-containing ligands.

关键词： Collision-induced dissociation Ion-mobility spectrometry Collision cross section Density functional theory molecular dynamics simulation

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Chinese Journal of Integrative Medicine 2009年第5期15卷 371-376页

作者：郑春松叶蕻芝徐筱杰刘献祥 Fujian Academy of Integrative Medicine Fujian College of Traditional Chinese Medicine College of chemistry and molecular Engineering Peking University

Objective： To study the pharmacological properties of Tougu Xiaotong Granule （透骨消痛颗粒, TGXTG） in preventing and treating knee osteoarthritis （KOA） at the molecular level. Methods： The computational methods, including principal component analysis, molecular docking, target-ligand space distribution, and the predictions of absorption, distribution, metabolism, excretion and toxicity （ADMET）, were introduced to characterize the molecules in TGXTG. Results： The structural properties of molecules in TGXTG were more diverse than those of the drug/drug-like molecules, and TGXTG could interact with significant target enzymes related to KOA. In addition, the cluster of effective components was preliminarily identified by the target-ligand space distributions. As to the results of ADMET properties, some of them were unsatisfactory, and were merely regarded as references here. Conclusion： Based on this computational pharmacology study, TGXTG is a broad- spectrum recipe inhibiting many important target enzymes, which could effectively postpone the degeneration of cartilage by coordinately inhibiting the biological effects of cytokines, matrix metallopeptidase 3, and oxygen free radicals.

关键词： Tougu Xiaotong Granule osteoarthritis chemical space virtual screening computational pharmacology

KAPtain in charge of multiple missions: Emerging roles of KAP1

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World Journal of biological chemistry 2014年第3期5卷 308-320页

作者： Chun-Ting Cheng Ching-Ying Kuo David K Ann department of molecular pharmacology Beckman Research Institute Irell and Manella Graduate School of biological Sciences Beckman Research Institute

KAP1/TRIM28/TIF1β was identified nearly twenty years ago as a universal transcriptional co-repressor because it interacts with a large KRAB-containing zinc finger protein(KRAB-ZFP) transcription factor family. Many studies demonstrate that KAP1 affects gene expression by regulating the transcription of KRAB-ZFP-specific loci, trans-repressing as a transcriptional co-repressor or epigenetically modulating chromatin structure. Emerging evidence suggests that KAP1 also functions independent of gene regulation by serving as a SUMO/ubiquitin E3 ligase or signaling scaffold protein to mediate signal transduction. KAP1 is subjected to multiple post-translational modifications(PTMs), including serine/tyrosine phosphorylation, SUMOylation, and acetylation, which coordinately regulate KAP1 function and its protein abundance. KAP1 is involved in multiple aspects of cellular activities, including DNA damage response, virus replication, cytokine production and stem cell pluripotency. Moreover, knockout of KAP1 results in embryonic lethality, indicating that KAP1 is crucial for embryonic development and possibly impacts a wide-range of(patho)physiological manifestations. Indeed, studies from conditional knockout mouse models reveal that KAP1-deficiency significantly impairs vital physiological processes, such as immune maturation, stress vulnerability, hepatic metabolism, gamete development and erythropoiesis. In this review, we summarize and evaluate current literatures involving the biochemical and physiological functions of KAP1. In addition, increasing studies on the clinical relevance of KAP1 in cancer will also be discussed.

关键词： KRAB domain-associated protein 1 Transcriptional co-repressor Post-translational modification Chromatin remodeling KRAB-containing zinc finger protein

Ratio quantification of gene dosage by Agilent 2100 Bioanalyzer for detection of somatic gene deletions

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Advances in biological chemistry 2012年第1期2卷 70-75页

作者： Peter Hwu Qiang Liu Yafan Wang Linling Chen Yawen Cheng Wanru Lin Yun Yen department of molecular pharmacology City of Hope Comprehensive Cancer Center Duarte USA Institute of Medicine Chung Shan Medical University Taichung Chinese Taipei Translational Research Core Laboratory City of Hope Comprehensive Cancer Center and Beckman Research Institute Duarte USA

We applied the Agilent 2100 Bioanalyzer, a microfluidics-based electrophoresis instrument, and introduced an accurate and consistent parameter, the relative product yield ratio (ROY), to detect somatic gene deletions in tumor cells. Briefly for such purpose, the Agilent 2100 Bioanalyzer quantified the ROY of a target gene to an endogenous internal control, both of which were initially co-amplified by Robust-Dosage PCR (RD- PCR). Herein, we extensively validated this approach. We first tested the effect of well positions on the Agilent DNA chip. We found that no matter which wells the samples were loaded in, the ROY was consistent with coefficient of variation (CV) < 2%. Then we tested the effect of product concentrations that varied 8-fold, and the ROY was also consistent with CV < 3.5%. Furthermore, we applied this approach to identify six somatic KRAS deletions in non-small cell lung cancer patients, confirming our previous findings. Thus, the Agilent 2100 Bioanalyzer is simple, accurate, quick, and ultimately able to replace conventional gel electrophoresis for the detection of somatic gene deletions.

关键词： Electrophoresis Gene Deletion Detection Agilent 2100 Bioanalyzer RD-PCR NSCLC

基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计（英文）

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中国药理学与毒理学杂志 2017年第10期31卷 945-946页

作者： John J TESMER Helen V WALDSCHMIDT Marie C CATO Renee BOULEY Osvaldo CRUZ-RODRIGUEZ Scott D LARSEN University of Michigan Life Sciences Institute Ann ArborMichigan 48109 USA department of biological Sciences Purdue UniversityWest Lafayette Indiana 47907 USA University of Michigan Valteich Medicinal chemistry Core Ann ArborMichigan 48109 USA

G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell *** timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained *** GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human *** GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease ***2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,*** lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational *** have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted *** then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for *** a"hybrid"inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal *** analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes.

关键词： herat failure GPCR GPCR kinase paroxetine drug design X-ray crystallography

刍议质谱技术发现新型蛋白质翻译后修饰研究在化学与生物学教学中的应用

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大学化学 2021年第6期36卷 185-193页

作者：王志鹏张璇车子良蒋振雄马新雨 Division of Genetics Department of MedicineBrigham and Women’s HospitalDepartment of Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolBostonMA 02115USA. department of chemistry Texas A&M UniversityCollege StationTX 77840USA. 清华大学化学系北京100084 清华大学生命学院北京100084 department of Mathematics Harvard UniversityMA 02138USA. department of Biology Texas A&M UniversityCollege StationTX 77840USA.

随着质谱技术的不断发展,质谱技术已经被广泛应用于化学、材料、生命科学等众多领域,特别是其在生物化学与化学生物学领域的应用极大扩展了研究人员对于蛋白质翻译后修饰的认知。本文从基本的质谱原理入手,着重探讨了质谱技术在以组蛋... 详细信息

随着质谱技术的不断发展,质谱技术已经被广泛应用于化学、材料、生命科学等众多领域,特别是其在生物化学与化学生物学领域的应用极大扩展了研究人员对于蛋白质翻译后修饰的认知。本文从基本的质谱原理入手,着重探讨了质谱技术在以组蛋白为模式蛋白的赖氨酸翻译后修饰的发现过程,并展示如何将基础有机化学和生物化学知识融入前沿科学研究。本文通过梳理不同的研究逻辑下质谱技术在蛋白翻译后修饰的研究中发挥的作用,旨在引导学生建立起将基础教学内容与实际应用相联系的意识及思维模式。

关键词：质谱技术串联质谱翻译后修饰生物化学