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： 010--80726688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。

Research Interest: Reseach@Qi Group

Our lab is focused on the interface of biocatalysis, natural product biomimetic synthesis and biologically valuable molecule discovery.  We are encouraged by the rapid and efficient construction of molecular complexity from simple precursors in living organisms by enzymatic pathway. On the microcosmic molecular level, enzyme catalyzed organic bond formation provided fundamental details of the molecular activation between catalyst and substrates through either non-bonded or covalent-bonded interactions. Inspired by the three-dimensional structure of the active binding residues of the enzyme pocket, we are interested in developing organic small molecule catalyst for stereoselective construction of chemical bonds that otherwise tough to access.  Privileged coordination of transition structure geometries and molecular recognition that control selectivity will be explored in details by computational calculation and chemical kinetics. The utility of these small molecule catalysts will be demonstrated by the synthesis of a variety of important biologically interesting compounds through environmentally friendly organocascade process that involve the formation of several chemical bonds and stereogenic centers simultaneously with excellent stereoselectivity. Structurally complex natural products are naturally produced in microorganisms through a series of elaborate biological pathways, so its biomimetic synthesis will be incorporated with organocascade catalysis in the lab. Besides discovery of small molecule catalysis and natural product biomimetic synthesis, we are also interested in developing novel reagents for practical transformations to rapidly assemble unnatural complex molecules. The combination of chemical synthesis and biosynthesis of biologically valuable molecules is an important part of our pursuits for exciting discoveries of biomaterials, chemical biology as well as pharmaceutical agents to solve serious health problem in living system.

Overall, the inspiration from natural living system to develop small molecule catalyst, organocascade assembling of complex molecule will eventually result in discovery of novel bio-valuable molecules, which in turn serve as significant regulatory tools for a variety of biological pathways in living system. During this conceivably “functional cycle”, small molecule and living organism can be thought of as complementary forces that interact to form a dynamic system in which each could promote mutually by the other. We presumptively demonstrate this as “Functional Reincarnation of Organic Molecule”, thereupon we bear persistent enthusiasm for the pursuit of ideal discovery of novel molecules and interpretation their bioactive mechanism of act.

Total Synthesis of Natural product:

Inspired by the rapid and efficient construction of molecular complexity from simple precursors in natural living system by enzymatic pathway, our lab is mainly focused on the biocatalysis development and the utilization of biomimetic synthesis of natural products and biologically valuable small molecules. The utility of biomass-derived building blocks will be demonstrated by the synthesis of a variety of natural products through environmentally friendly organocascade process that involve the formation of several chemical bonds and stereogenic centers simultaneously with excellent stereoselectivity. Structurally complex natural products are naturally produced in microorganisms through a series of elaborate biological pathways, so its biomimetic synthesis will be incorporated with organocascade transformations in the lab. Furthermore, the mode of action studies are highly investigated in the lab to reveal the role that natural products have and will continue to play in mapping important biochemical networks and identification of novel therapeutic targets.

Medicinal Chemistry:

The use of small molecules to probe systematic and disease-associated biological phenomena is an important aspect of our research. Motivated by the urgent and valuable applications of small molecules in therapeutics and biomedical research, we are devoted to synthesizing new organic, inorganic, and organometallic molecules that applicable to a wide variety of biological areas conducted at NIBS. We are working on the molecule discovery and collection through synthetic method development with the aim of expanding chemical diversity in novel ways.  Molecules synthesized in the our lab are inherently integrated for the purpose of examining their biological properties. The outcomes of this biological evaluation and the performance in biological screening are the main guidance for further synthesis design. After a range of chemicals is screened against a particular drug target or disease model, and the qualified “hits” chemicals are concentrated and analyzed. Commonalities among the different chemical groups are studied as they are often reflective of a particular chemical subunit. Additional chemical synthesis will be enforced to extend out the chemical library through “activity-oriented synthesis” in that particular subspace by generating more compounds with subtle and profound modifications. This new selection of compounds within this narrow range are further investigated and then taken on to more sophisticated models for further validation. Chemical compounds need to satisfy a variety of constraints before they become pharmaceutical candidate, including solubility, oral bioavailability, cell membrane permeability, liver enzyme activity, plasma protein binding, penetration of the blood-brain barrier, toxicity, and many others. We are focusing on the structure design to improve molecular properties that are not limited to known druggability rules.

High-Throughput Screening:

HTS is a drug-discovery process widely used in the pharmaceutical companies and biomedical research institutes. Using robotics, data processing and control software, liquid handling devices and sensitive detectors, HTS conduct extremely scalable assay to test the biological or biochemical activity of a large number of small molecules for discovering active agents for receptors, enzymes, ion-channels or other pharmacological targets in the molecular and cellular level of biomolecular pathway. Typically, HTS assays are performed in microtiter plates with a 96 or 384 well format. HTS is one of main facilities in our lab to provide comprehensive services including the use of HTS technology, compounds in various libraries, a database of results from screens and lead optimization. On a collaborative basis, HTS has the capability to support cellular and biochemical assays using absorbance, fluorescent kinetics, fluorescence resonance energy transfer, AlphaScreen, bioluminescence and cellular fluorescence imaging. In addition, HTS has expertise in adapting those biological and biochemical bench-top assays into high-throughput screening settings.HTS librariesare designed for diversity that not only limited to specific pharmacophore, bioactivities or specific focused collections. Biomedical and clinical property profiles will be highly considered for the library design and construction process.