雷晓光博士
- 基本信息
- 教育经历
- 工作经历
- 研究概述
- 发表文章
雷晓光 博士
北京生命科学研究所高级研究员
Xiaoguang Lei, Ph.D. Associate Investigator, NIBS, Beijing, China
Phone：010-80704786
Fax： 010-80704785
E-mail：leixiaoguang@nibs.ac.cn
教育经历
Education:
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2001 |
北京大学，化学与分子工程学院，化学学士学位 |
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B.S. in Chemistry, Peking University, Beijing, China |
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2006 |
美国波士顿大学，化学系，有机化学博士学位 |
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Ph.D. in Organic Chemistry, Boston University, Boston, USA |
工作经历
Professional Experience:
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2013-present |
北京生命科学研究所高级研究员 |
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Associate Investigator and Director of Chemistry Center, NIBS |
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2008-2012 |
北京生命科学研究所研究员, 化学中心主任 |
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Assistant Investigator and Director of Chemistry Center, NIBS |
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2006- 2008 |
美国哥伦比亚大学，美国斯隆-凯特林癌症研究中心，博士后 |
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Postdoctoral Fellow, Columbia University and Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA |
研究概述：
小分子影响了许多重要的生物过程， 因此它们可以被认为是“中心法则”的另一个重要的组成成分。具有生物活性的小分子可以是通过自然进化选择的天然产物，也可以是通过有机合成制造的药物分子和用于研究生物进程的化学探针。 因此有机合成是化学学科中的重要分支，与药物研发，以及生命科学研究密切相关。当前，我们急需应用新的小分子去帮助研究已知的生物反应机理，去发现尚未被阐明的生物作用机理，去验证全新的生物药物靶点，和去解决重大的医学难题。特别是当前创新型药物研究进入到一个多学科、多技术协作的新时代。其中化学，特别是有机合成，药物化学与化学生物学，和生命科学的结合是满足创新型药物研发的先决条件。因此，我们实验室的主要研究方向包括以下三个方面：
1）对于具有重要生物功能和复杂结构的天然产物的全合成；
2）运用天然产物和其他具有生物活性的小分子作为分子探针进行化学生物学研究，从而发现新的生物靶点和阐明新的生物作用机制；
3）寻找和发现新的药物靶点，利用药物化学手段设计并且合成相关小分子进行创新药物的研究。
4）发展新一代的生物正交反应，并且应用在化学生物学研究中。
Research Description
Many critical biological processes are conducted by small molecules and so they can arguably be regarded as another essential component of the “central dogma” of molecular biology. Biologically meaningful small molecules may be natural products, which are discovered by nature through many cycles of diversity generation and natural selection, or they may be prepared through organic synthesis for the development of drug candidates or chemical probes to study life’s processes. Therefore, organic synthesis is an important discipline that continues to play a vital role in drug discovery and in the allied fields of medicine and biology. New small molecules are needed to function as probes to further study the known biological pathways, to discover novel pathways and interactions, to validate potential drug targets, and to treat unmet medical needs as drugs. Accordingly, the central theme of our research focuses on the efficient synthesis of these small molecules, as well as the subsequent biological evaluations of these molecules applying medicinal chemistry and chemical biology approaches. We also hope to facilitate the synergy between synthetic chemistry and biological sciences at NIBS by creating a research environment in which new scientific collaborations are possible.
Publications
1. Li, Q.; Dong, T.; Liu, X.; Lei, X.* “A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether” J. Am. Chem. Soc. 2013, DOI: 10.1021/ja401989p.
2. Li, C.; Dong, T.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B” Chem. Sci. 2013, 4, 1163-1167.
3. Wang, G.; Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.*; Wang, X.* “Small Molecule Activation of the TRAIL Receptor DR5 in Human Cancer Cells” Nat. Chem. Biol. 2013, 2, 84-90. (News stories describing this work were highlighted inChem. & Eng. News 2013, 2, 37; Nature Asia 2012, December 24).
4. Huang, J.; Lei, X.* “A Nature-inspired Concise Synthesis of (+)-ent-Chromazonarol” Sci. China Chem. 2013, 56, 349-353.
5. Li, H.; Wang, X.; Hong, B.; Lei, X.* “Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (-)-Lycojapodine A” J. Org. Chem. 2013, 78, 800-821. (Featured and Cover Article).
6. Li, C.; Li, X.; Wang, X.; Lei, X.* “Diversity-Oriented Synthesis of Bicyclic Ring Systems via a Conjugate Addition/Aldol/RCM Process” Sci. China Chem. 2013, 56, 337-341.
7. Li, C.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses of (-)-Gochnatiolides A-C and (-)-Ainsliadimer B” J. Am. Chem. Soc. 2012, 134, 12414-12417.
8. Lei, X.*; Li, H. “Selective Alkene Metathesis in the Total Synthesis of Complex Natural Product” Top. Curr. Chem. 2012, 327, 163-196.
9. Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.;Lei, X.*; Wang, X.* “Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase” Cell 2012, 148, 213-227. (News stories describing this work were highlighted in Chem. & Eng. News 2012, 5, 40; Nature China 2012, February 1; Asian Scientist 2012, January31; and Nature Reviews Molecular Cell Biology, 2012, Feb. 8).
10. Li, H.; Wang, X.; Lei, X.* “Total Syntheses of Lycopodium Alkaloids (+)-Fawcettimine, (+)-Fawcettidine and (-)-8-Deoxyserratinine” Angew. Chem. Int. Ed. 2012, 51, 491-495; Angew. Chem. 2012, 124, 506-510.
11. Liao, D.; Li, H.; Lei, X.* “Efficient Generation of ortho-Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers” Org. Lett.2012, 14, 18-21.
12. Li, C.; Tu, S.; Wen, S.; Li, S.; Chang, J.; Shao, F.; Lei, X.* “Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C” J. Org. Chem. 2011, 76, 3566-3570.
13. Chou, T.; Dong, H.; Zhang, X.; Lei, X.; Hartung, J.; Zhang, Y.; Lee, H. L.; Wilson, R. M.; Danishefsky, S. J. * “Multifaceted Cytoprotection by Synthetic Polyacetylenes Inspired by the Ginseng-derived Natural Product Panaxytriol” Proc. Natl. Acad. Sci. USA 2011, 108, 14336-14341.
14. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.
15. Gong, Y.; Wang, X.; Wang, J.; Yang, Z.; Li, S.; Yang, J.; Liu, L.; Lei, X.*; Shao, F. * “Chemical Probing Reveals Insights into the Signaling Mechanism of Inflammasome Activation” Cell Res. 2010, 20, 1289-1305.
16. Han，Z.; Niu, T.; Chang, J.; Lei, X.; Zhao, M.; Wang, Q.; Cheng, W.; Wang, J.; Feng, Y.; Chai, J.* “Crystal structure of the FTO protein reveals basis for its substrate specificity” Nature 2010, 464, 1205-1209.
17. Lee, L. S.; Stephenson, K. K.; Fahey, J. W.; Parsons, T. L.; Lietman, P. S.; Andrade, A. S.; Lei, X. Yun, H.; Soon, G.H.; Shen, P.; Danishefsky, S. J.*; Flexner, C.* “Induction of Chemoprotective Phase 2 Enzymes by Ginseng and its Components” Planta Med. 2009; 75, 1129-1133
18. Lei, X.; Danishefsky, S. J.* “Efficient Synthesis of a Novel Resorcyclide as Anticancer Agent Based on Hsp90 Inhibition” Adv. Synth. Catal. 2008, 350, 1677-1681
19. Lei, X.; Dai, M.; Hua, Z.; Danishefsky, S. J.* “Biomimetic Total Synthesis of Tricycloillicinone and Mechanistic Studies Toward the Rearrangement of Prenyl Phenyl Ethers” Tetrahedron Lett. 2008, 49, 6383-6385
20. Ng, F.; Yun, H.; Lei, X.; Danishefsky, S. J.; Fahey, J.; Stephenson, K.; Flexner, C.; Lee, L.* “(3R,9R,10R)-Panaxytriol: a molecular-based nutraceutical with possible application to cancer prevention and treatment” Tetrahedron Lett. 2008, 49, 7178-7179
21. Peng, L. F.; Kim, S. S.; Matchacheep, S.; Lei, X.; Su, S.; Lin, W.; Runguphan, W.; Choe, W. H.; Sakamoto, N.; Beeler, A. B.; Porco, J. A., Jr.; Schreiber, S. L.* and Chung, R. T.* “Identification of Novel Epoxide Inhibitors of HCV Replication Using High-Throughput Screening.” Antimicrob. Agents Chemother. 2007, 51, 3756-3759.
22. Lei, X.; Porco, J. A., Jr.* “Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C.” J. Am. Chem. Soc. 2006, 128, 14790-14791. (News story describing this work was highlighted in Chem. & Eng. News 2006, 45, 9.)
23. Porco, J. A., Jr.*; Su, S.; Lei, X.; Bardhan, S.; Rychnovsky, S. D. “Total Synthesis and Structure Assignment of (+)-Hexacyclinol” Angew. Chem. Int. Ed. 2006, 45, 5790-5792; Angew. Chem. 2006, 118, 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006, 31, 11 and Nature 2006, 442, 492-493)
24. Lei, X.; Zaarur, N.; Sherman, M. Y.; Porco, J. A., Jr.* “Stereocontrolled Synthesis of a Complex Chemical Library via Elaboration of Angular Epoxyquinol Scaffolds.” J. Org. Chem. 2005, 70, 6474-6483.
25. Su, S.; Aquilano, D.; Arumugasamy, J.; Beeler, A. B.; Eastwood, E. L.; Giguere, J. R.; Lan, P.; Lei, X.; Min, G. K.; Yeager, A. R.; Zhou, Y.; Panek, J. S.; Snyder, J. K.; Schaus, S. E.; Porco, J. A., Jr.* “Convergent Synthesis of a Complex Oxime Library Using Chemical Domain Shuffling.” Org. Lett. 2005, 7, 2751-2754.
26. Lei, X.; Porco, J. A., Jr.* “Synthesis of a Polymer-Supported Anthracene and Its Application as a Dienophile Scavenger.” Org. Lett. 2004, 6, 795-798.
27. Lei, X.; Johnson, R. P.; Porco, J. A., Jr.* “Total Synthesis of the Ubiquitin-Activating Enzyme Inhibitor (+)-Panepophenanthrin.” Angew. Chem. Int. Ed. 2003, 42, 3913-3917; Angew. Chem. 2003, 115, 4043-4047. (This publication was highlighted as a “Hot Paper”.)
发表专利
Patents
1. Danishefsky, S. J.; Yun, H.; Chou, T.; Lei, X.; Sames, D. “Compounds and methods for treating cancer or neurotrophic disorder.” US2011/0124690
2. Danishefsky, S. J.; Chou, T.; Lei, X.; Yun, H.; Ng, F.; Hartung, J.; Sames, D. “Compounds, compositions and methods for reducing toxicity and treating or preventing diseases.” PCT Int. Appl. 2010, WO2010025272
3. Danishefsky, S. J.; Chou, T.; Lei, X. “Compounds, compositions and methods for treating or preventing diseases.” PCT Int. Appl. 2009, WO2009105123
4. Cottarel, G.; Gardner, T.; Lei, X.; Porco, J.; Schaus, S.; Wierzbowski, J. “Compositions and methods for potentiating antibiotic activity using an ATP receptor antagonist, coumarin, flavone, or terpene” PCT Int. Appl., 2008, WO2008019292
5. Danishefsky, S. J. Lei, X.; Yun, H.; Chou, T. “Compositions and methods using a panaxytriol compound in combination with a tubulin-binding drug for treating cancer or a neurotrophic disorder.” PCT Int. Appl. 2008, WO 2008103916
