基本信息
教育经历
工作经历
研究概述
发表文章

齐湘兵博士 化学中心主任

Xiangbing Qi, Ph.D.

Director of Chemistry Center

National Institute of Biological Science, Beijing

电话： 转8655
传真： 010-8070-8048
E-mail:qixiangbing@nibs.ac.cn

Homepage:http://qigroup.nibs.ac.cn/


教育经历
Education

2005-2009年美国德州大学西南医学中心生物化学系，有机化学博士学位
Ph.D. Organic Chemistry，Department of Biochemistry，University of Texas Southwestern Medical Center at Dallas
2001-2004年同济大学化学系，有机化学硕士学位
M.S. Organic Chemistry, Department of Chemistry, Tongji University
1997-2001年济南大学化学化工学院，应用化学学士学位
B.S. Applied Chemistry, School of Chemistry and Chemical Engineering, University of Jinan


工作经历
Professional Experience
2013年- 北京生命科学研究所化学中心主任
Director of Chemistry Center, National Institute of Biological Sciences, Beijing, China
2010-2013年 美国德州大学西南医学中心生物化学系，有机化学与药物化学博士后研究员
Postdoctoral Fellow, Organic Chemistry and Medicinal Chemistry, Department of Biochemistry，University of Texas Southwestern Medical Center at Dallas.
2009-2010年 美国伊利诺伊大学厄巴纳-香槟分校化学系，有机化学博士后研究员
Postdoctoral Fellow, Organic Chemistry，Department of Chemistry，University of Illinois at Urbana-Champaign.
2004-2005年 中科院上海有机所，有机合成/药物研发研究助理
Research Assistant, Organic synthesis/Medicinal chemistry，Shanghai Institute of Organic Chemistry, Chinese Academy of Science.


化学中心/齐湘兵实验室：Qi Group@NIBS
北京生命科学研究所化学中心齐湘兵实验室主要研究方向为具有生物活性的有机小分子合成与药物开发,天然药物分离纯化与结构分析鉴定，化学小分子库的构建和高通量筛选，天然小分子全合成和生物仿生合成，同时开发新型化学小分子探针用于鉴定药物新靶点并通过探索化学生物学新策略研究小分子与靶点的相互作用关系调控重要的生物学机理。我们实验室还为研究所的各实验室创建高质量的辅助平台,提供专业的化学服务并与生物实验室紧密合作开展前沿交叉课题，基于生物基础研究进展，结合现代药物研发的最新技术手段包括计算机辅助设计以及高通量筛选等，配以先进的仪器装备（NMR，LCMS，HPLC，GC/MS）协助各实验室开发全新的生物医药靶点并通过化学小分子探究与调控重要的生物学途径。我们课题组核心部分主要包括：化学合成实验室，分析检测实验室和高通量筛选实验室。我们将紧密地把有机合成，药物化学，化学生物学与生命科学相结合，从而为北京生命科学研究所建立起一套完善的化学服务与创新型药物研发平台和团队。

ResearchInterest: Reseach@Qi Group

Our lab is focused on the interfaceofbiocatalysis, natural product biomimetic synthesis and biologically valuablemolecule discovery.We are encouraged by the rapid and efficientconstruction of molecular complexity from simple precursors in living organismsby enzymatic pathway. On the microcosmic molecular level, enzyme catalyzedorganic bond formation provided fundamental details of the molecular activationbetween catalyst and substrates through either non-bonded or covalent-bondedinteractions. Inspired by the three-dimensional structure of the active bindingresidues of the enzyme pocket, we are interested in developing organic smallmolecule catalyst for stereoselective construction of chemical bonds thatotherwise tough to access. Privileged coordination of transitionstructure geometries and molecular recognition that control selectivity will beexplored in details by computational calculation and chemical kinetics. Theutility of these small molecule catalysts will be demonstrated by the synthesisof a variety of important biologically interesting compounds throughenvironmentally friendly organocascade process that involve the formation ofseveral chemical bonds and stereogenic centers simultaneously with excellentstereoselectivity. Structurally complex natural products are naturally producedin microorganisms through a series of elaborate biological pathways, so itsbiomimetic synthesis will be incorporated with organocascade catalysis in thelab. Besides discovery of small molecule catalysis and natural productbiomimetic synthesis, we are also interested in developing novel reagents forpractical transformations to rapidly assemble unnatural complex molecules. Thecombination of chemical synthesis and biosynthesis of biologically valuablemolecules is an important part of our pursuits for exciting discoveries ofbiomaterials, chemical biology as well as pharmaceutical agents to solveserious health problem in living system.
Overall, the inspiration from naturalliving system to develop small molecule catalyst, organocascade assembling ofcomplex molecule will eventually result in discovery of novel bio-valuablemolecules, which in turn serve as significant regulatory tools for a variety ofbiological pathways in living system. During this conceivably “functionalcycle”, small molecule and living organism can be thought of as complementaryforces that interact to form a dynamic system in which each could promotemutually by the other. We presumptively demonstrate this as “FunctionalReincarnation of Organic Molecule”, thereupon we bear persistent enthusiasm forthe pursuit of ideal discovery of novel molecules and interpretation theirbioactive mechanism of act.

Total Synthesis of Natural product:

Inspired by the rapid and efficient construction of molecularcomplexity from simple precursors in natural living system by enzymaticpathway, our lab is mainly focused on the biocatalysis development and theutilization of biomimetic synthesis of natural products and biologicallyvaluable small molecules. The utility of biomass-derived building blocks willbe demonstrated by the synthesis of a variety of natural products throughenvironmentally friendly organocascade process that involve the formation ofseveral chemical bonds and stereogenic centers simultaneously with excellent stereoselectivity.Structurally complex natural products are naturally produced in microorganismsthrough a series of elaborate biological pathways, so its biomimetic synthesiswill be incorporated with organocascade transformations in the lab. Furthermore,the mode of action studies are highly investigated in the lab to reveal therole that natural products have and will continue to play in mapping importantbiochemical networks and identification of novel therapeutic targets.

MedicinalChemistry:
The use of small molecules toprobe systematic and disease-associated biological phenomena is an importantaspect of our research. Motivated by the urgent and valuable applications ofsmall molecules in therapeutics and biomedical research, we are devoted tosynthesizing new organic, inorganic, and organometallic molecules thatapplicable to a wide variety of biological areas conducted at NIBS. We areworking on the molecule discovery and collection through synthetic methoddevelopment with the aim of expanding chemical diversity in novelways.Molecules synthesized in the our lab are inherently integratedfor the purpose of examining their biological properties. The outcomes of thisbiological evaluation and the performance in biological screening are the mainguidance for further synthesis design. After a range of chemicals is screenedagainst a particular drug target or disease model, and the qualified “hits”chemicals are concentrated and analyzed. Commonalities among the differentchemical groups are studied as they are often reflective of a particularchemical subunit. Additional chemical synthesis will be enforced to extend outthe chemical library through “activity-oriented synthesis” in that particularsubspace by generating more compounds with subtle and profound modifications.This new selection of compounds within this narrow range are furtherinvestigated and then taken on to more sophisticated models for furthervalidation. Chemical compounds need to satisfy a variety of constraints beforethey become pharmaceutical candidate, including solubility, oralbioavailability, cell membrane permeability, liver enzyme activity, plasmaprotein binding, penetration of the blood-brain barrier, toxicity, and manyothers. We are focusing on the structure design to improve molecular propertiesthat are not limited to known druggability rules.

High-ThroughputScreening:
HTS is a drug-discoveryprocess widely used in the pharmaceutical companies and biomedical researchinstitutes. Using robotics, data processing and control software, liquidhandling devices and sensitive detectors, HTS conduct extremely scalable assayto test the biological or biochemical activity of a large number of smallmolecules for discovering active agents for receptors, enzymes, ion-channels orother pharmacological targets in the molecular and cellular level ofbiomolecular pathway. Typically, HTS assays are performed in microtiter plateswith a 96 or 384 well format. HTS is one of main facilities in our lab toprovide comprehensive services including the use of HTS technology, compoundsin various libraries, a database of results from screens and lead optimization.On a collaborative basis, HTS has the capability to support cellular andbiochemical assays using absorbance, fluorescent kinetics, fluorescenceresonance energy transfer, AlphaScreen, bioluminescence and cellularfluorescence imaging. In addition, HTS has expertise in adapting thosebiological and biochemical bench-top assays into high-throughput screeningsettings.HTS librariesare designed for diversity thatnot only limited to specific pharmacophore, bioactivities or specific focusedcollections. Biomedical and clinical property profiles will be highlyconsidered for the library design and construction process.

部分发表文章
Selected Publications
1. Lei Zhang, Ye Zhang, Wenting Li, Xiangbing Qi, “Total Synthesis of (-)-Alstofolinine A through a Furan Oxidation/Rearrangement and Indole Nucleophilic Cyclization Cascade” Angew. Chem. Int. Ed. 2019, https://doi.org/10.1002/anie..
2. Yu Zhou, Yuanxun Wang, Pengfei Li, Xi-Ping Huang, Xiangbing Qi, Yunfei Du, and Niu Huang. “Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor–Ligand Interactions” ACS Med. Chem. Lett., 2018, 9 (10), pp 1019–1024.
3. Chao Wei, Xiao Han, Danwei Weng, Qiru Feng, Xiangbing Qi, Jin Li & Minmin Luo. “Response dynamics of midbrain dopamine neurons and serotonin Interactions neurons to heroin, nicotine, cocaine, and MDMA” Cell Discovery， 4 : 60 (2018) 1019–1024.
4. Aaron Nash, Xiangbing Qi, Pradip Maity, Kyle Owens, and Uttam K. Tambar*. “Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)‐Lundurine?A” Angew. Chem. Int. Ed., 2018, 57, 6888-6891.
5. Rui Lin, Qiru Feng, Peng Li, Ping Zhou, Ruiyu Wang, Zhe Liu, Zhiqiang Wang, Xiangbing Qi, Nan Tang, Feng Shao, Minmin Luo, “A hybridization-chain-reaction-based method for amplifying immunosignals” Nature Methods, 2018 (4), 275
6. Xuekai Zhang, Gang Lu, Meng Sun, Madhu Mahankali, Yanfei Ma, Mingming Zhang, Wangde Hua, Yuting Hu, Qingbing Wang, Jinghuo Chen, Gang He, Xiangbing Qi*, Weijun Shen, Peng Liu, Gong Chen，“A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp 3 C? H arylation”， Nature Chemistry，2018（10）, 540-548
7. Xueyan Ma, Peixue Li, Peihao Chen, Jinhui Li, Hongling Huang, Chao Wang, Wenjing Li, Jianping Ding, Yun Zhao, Fa-Xing Yu, Xiangbing Qi*, Lei Zhang，“Staurosporine targets the Hippo pathway to inhibit cell growth” Journal of Molecular Cell Biology, 2018, 10, 267-269
8. Yanli Wang, Yuze Sun, Ran Cao, Dan Liu, Yuting Xie, Li Li, Xiangbing Qi*, Niu Huang，“In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery” J. Med. Chem., 2017, 60 (20), pp 8552-8564
9. Shih-Chia Tso, Mingling Lou, Wen-Jun Gui , Cheng-Yang Wu, Jacinta L. Chuang, Lorraine K. Morlock, Noelle S. Williams, R. Max Wynn, Xiangbing Qi* and David T. Chuang* “Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-targeting Pyruvate Dehydrogenase Kinase Inhibitors” J. Med. Chem., 2017, 60 (3), 1142-1150.
10. Yaling Wu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, Haijiao Zhao, Peihao Chen, Xiangbing Qi and Eric Erquan Zhang. “Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals”, Cell Metabolism, 2017, 25 (1), 73-85.
11. Shih-chia Tso*, Xiangbing Qi*, Wen-Jun Gui, Jacinta L. Chuang, Lorraine K. Morlock, Amy L. Wallace, Kamran Ahmed, Sunil Laxman, Philippe M. Campeau, Brendan H. Lee, Susan M. Hutson, Benjamin P. Tu, Noelle S. Williams, Uttam K. Tambar, R. Max Wynna, and David T. Chuang. , “Structure-based Design and Mechanisms of Allosteric Inhibitors for Mitochondrial Branched-chain α-Ketoacid Dehydrogenase Kinase.” Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 9728-9733. (* Equal Contribution)
12. Feng Cai, Xiaotao Pu, Xiangbing Qi, Joseph. M. Ready*. “Allenes in Asymmetric Catalysis: Asymmetric Addition of Boronic Acid to α-ketoesters Catalyzed by Allene-Containing Rhodium-Phosphine Catalyst”. J. Am. Chem. Soc., 2011, 133, 18066-18069.
13. Xiangbing Qi, Hongli Bao, Uttam K.Tambar*. “Total Synthesis of (±)-Trigonoliimine C via Oxidative Rearrangement of an Unsymmetrical Bis-Tryptamine”, J. Am. Chem. Soc. 2011, 133, 10050-10053.
14. Hongli Bao, Xiangbing Qi, Uttam K.Tambar*. “Catalytic Enantioselective [2,3]-Rearrangements of Amine N-Oxides ”, J. Am. Chem. Soc. 2011, 133, 1206-1208.
15. Xiangbing Qi, Grant T. Rice, Manjinder S. Lall, Mark S. Plummer, M. Christina White* “Diversification of a β-lactam Pharmacophore via Allylic C–H Amination: Accelerating Effect of Lewis Acid co-catalyst”, Tetrahedron, 2010, 66, 4816-4826.
16. Xiaotao Pu, Xiangbing Qi, Joseph. M. Ready*. “Allenes in Asymmetric Catalysis: Asymmetric Ring Opening of meso-Epoxides Catalyzed by Allene-Containing Phosphine Oxides” J. Am. Chem. Soc. 2009, 131, 10364-10365.
17. Xiangbing Qi, Joseph. M. Ready*. “Synthesis of Cyclopentenones from Cyclopropanes and Silyl Ynol Ethers” Angew. Chem. Int. Ed. 2008, 47, 7068-7070.
18. Xiangbing Qi, Joseph. M. Ready*. “Copper-Promoted Cycloaddition of Diazocarbonyl Compounds with Copper Acetylides” Angew. Chem. Int. Ed. 2007, 46, 3242-3244.

专利Patents
1. David T. Chuang, Shih-Chia Tso, Xiangbing Qi, Wen-Jun Gui, Cheng-Yang Wu, Jacinta L. Chuang, Uttam K. Tambar, R. Max Wynn “Inhibitors of mitochondrial pyruvate dehydrogenase kinase isoforms 1-4 and uses thereof” USA1
2. Wenhui Li, Xiangbing Qi, Huan Yan, Yang Liu, Zhiqiang Wang, Bo Peng, Lei Zhang，“Polymeric Bile Acid Derivatives Inhibit Hepatitis B and D Virus and NTCP Transport”. USA1。
3. Niu Huang, Xiangbing Qi, Yanli Wang, Yuze Sun. “Kinase Inhibitors”， WOA1
4. Xiangbing Qi, Mingliang Lou, Enlong Wu, Peihao Chen, Qingcui Wu, “Dihydroxyphenyl Sulfonylisoindoline Derivatives”, WOA1
5. Erquan Zhang, Xiangbing Qi, Dapeng Ju, Haijiao Zhao, Long Mei, Zhiqiang Wang, Qingcui Wu, “Adenosine Analog and its use in Regulating the Circadian Clock”
PCT/CN2017/071903