Scientific Research
Huchen Zhou
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Overview
Huchen Zhou, Ph.D.
B.S., Fudan University, Department of Chemistry, 1997
Ph.D., Princeton University, Department of Chemistry, 2003
Postdoctoral Research, Yale University, Department of Chemistry, 2003-2005
Joined Shanghai Jiao Tong University faculty in 2007
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Members
Qingqing Meng, Ph.D.
B.S. and Ph.D., Fudan University, Department of Chemistry
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Research Field
Design and synthesis of small molecules as probes of physiologically important cellular processes and as modulators of pathological conditions, with a focus on infective diseases and cancer. (Organic synthesis; Computer-aided drug design; Chemical biology)
The interactions between small organic molecules and biological supramolecules are the fundamental events that result in the regulation of cellular activities. Small molecules are designed to interact with biological supramolecules that play important roles in cellular signal transduction pathways, thus leading to the elucidation of cullular mechnisms and the manipulation of celluar activities.
Protein-protein and ligand-protein interactions related to human diseases such as cancer and infective diseases are the main focus of our research. Novel chemical structures aimed to disrupt these interactions are designed by molecular modeling, and organic synthesis was used as the essential tool to obtain these molecules. The ultimate goal is toward the discovery of new therapeutic compounds and novel drug targets.
Our current focus is on the design and synthesis of small molecules as chemical probes or as anti-infective and anti-cancer drug candidates. The current projects include: Design and synthesis of cysteine protease inhibitors and aminoacyl-tRNA synthetase inhibitors as anti-infective and anti-cancer agents; Design and synthesis of chemical probes for chemical biology research aiming to reveal novel mechanism of action and new biological targets.
We welcome students and young researchers who are interested in our research to join us.
We teach undergraduate “Medicinal Chemistry?
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Publications & Patents
1. Ding, D.; Meng, Q; Gao, G.; Zhao, Y.; Wang, Q.; Nare, B.; Jacobs, R.; Rock, F.; Alley, M. R. K.; Plattner, J. J.; Chen, G. Q.; Li, D.; Zhou, H.* “Design, synthesis, and structure-activity relationship of Trypanosoma brucei leucyl-tRNA synthetase inhibitors as antitrypanosomal agents.?J. Med. Chem. 2011, in press, DOI: 10.1021/jm101225g.
2. Gu, Z.; Liu, C.; Wu, S.; Zhao, M.; Xu, H.; Liu, W.; Zhou, H.; Chen, G.; Wu, Y. ?PU.1 directly regulates retinoic acid-induced expression of RIG-G in leukemia cells.?FEBS Lett. 2011, in press, DOI: 10.1016/j.febslet.2010.12.021.
3. Wu, Y.; Zhou, H.; Chen, G “Molecular mechanisms of leukemia-associated protein degradation.?Front. Med. China 2010, 4, 363-370.
4. Ding, D.; Zhao, Y.; Meng, Q.; Xie, D.; Nare, B.; Chen, D.; Bacchi, C. J.; Yarlett, N.; Zhang, Y. K.; Hernandez, V.; Xia, Y.; Freund, Y.; Abdulla, M.; Ang, K. H.; Ratnam, J.; McKerrow, J. H.; Jacobs, R. T.; Zhou, H.*; Plattner, J. J. “Discovery of novel benzoxaborole-based potent antitrypanosomal agents.?ACS Med. Chem. Lett. 2010,1,165-169.
5. Ye, L.; Ding, D.; Feng, Y.; Xie, D.; Wu, P.; Guo, H.; Meng, Q.; Zhou, H.* “Convenient and versatile synthesis of formyl-substituted benzoxaboroles.?Tetrahedron 2009, 65, 8738-8744.
6. Lu, Q.; Longo, F. M.; Zhou, H.; Massa, S. M.; Chen, Y. “Signaling through Rho GTPase pathway as viable drug target.?Curr. Med. Chem. 2009, 16,1355-1365.
7. Akama, T.; Baker, S. J.; Zhang, Y. K.; Hernandez, V.; Zhou, H.; Sanders, V.; Freund, Y.; Kimura, R.; Maples, K. R.; Plattner, J. J. “Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.?Bioorg. Med. Chem. Lett. 2009, 19, 2129-2132.
8. Chen, W.; Huang, T.; He, X.; Meng, Q.; You, D.; Bai, L.; Li, J.; Wu, M.; Li, R.; Xie, Z.; Zhou, H.; Zhou, X.; Tan, H.; Deng, Z. “Charaterization of the polyoxin biosynthesis gene cluster from Streptomyces cacaoi and engineered production of polyoxin H.?J. Biol. Chem. 2009, 284, 10627-10638.
9. Zhou, Y.; Meng, Q.; You, D.; Li, J.; Chen, S.; Ding, D.; Zhou, X.; Zhou, H.*; Bai, L.*; Deng, Z. “Selective removal of aberrant extender units by a type II thioesterase for efficient FR-008/candicidin biosynthesis in streptomyces sp. strain FR-008.?Appl. Environ. Microbiol. 2008, 74, 7235-7242.
10. Rock, F. L.; Mao, W.; Yaremchuk, A.; Tukalo, M.; Crepin, T.; Zhou, H.; Zhang, Y. K.; Hernandez, V.; Akama, T.; Baker, S. J.; Plattner, J. J.; Shapiro, L.; Martinis, S. A.; Benkovic, S. J.; Cusack, S.; Alley, M. R. K. “An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.?Science, 2007, 316, 1759-1761.
11. Baker, S. J.; Zhang, Y. K.; Akama, T.; Lau, A.; Zhou, H.; Hernandez, V.; Mao, W.; Alley, M. R. K.; Sanders, V.; Plattner, J. J. “Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), for the potential treatment of onychomycosis.?J. Med. Chem. 2006, 49, 4447-4450.
12. Zhou, H.; Baldini, L.; Hong, J.; Wilson, A. J.; Hamilton, A. D. “Pattern-recognition of proteins based on an array of functionalized porphyrins?J. Am. Chem. Soc. 2006, 128, 2421-2425.
13. Zhou, H.; Baldini, L.; Ennis, E.; Jain, R.; Sebti, S. M.; Wang, D-A; Blaskovich, M. A.; Hamilton, A. D. “Structure-Activity studies of a library of potent calix[4]arene based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation?Org. Biomol. Chem. 2006, 4, 2376-2386.
14. Zhou, H. and Hamilton, A. D. “Protein surface recognition.? in “Encyclopedia of Supramolecular Chemistry? Taylor & Francis, 2006, 1: 1, 1-13.
15. Zhou, H.; Ding, D.; Feng, Y.; Ye, L.; Jacobs, R.; Orr, M.; Wring, S.; Chen, D.; Hernandez, V.; Zhang, Y. K.; Plattner, J. J. “Boron-containing small molecules as anti-protozoal agents.?PCT Int. Appl. WO 2010045505, 2010.
16. Jacobs, R.; Orr, M.; Wring, S.; Chen, D.; Zhou, H.; Ding, D.; Feng, Y.; Ye, L.; Hernandez, V. S.; Zhang, Y. K.; Plattner, J. J. “Boron-containing small molecules as anti-protozoal agents.?PCT Int. Appl. WO 2010045503, 2010.
17. Baker, S. J.; Hernandez, V. S.; Sharma, R.; Nieman, J. A.; Akama, T.; Zhang, Y. K.; Plattner, J. J.; Alley, M. R. K.; Singh, R.; Xia, Y.; Zhou, H.; Mohammad, R.; Keramane, E. M.; Lu, X.; Ha, M.; Phillips, J. G.; “Boron-containing Small Molecules.?WO 2008157726, 2008.
18. Akama, T.; Baker, S. J.; Hernandez, V. S.; Plattner, J. J.; Zhang, Y. K.; Zhou, H.; “Microorganism killing compounds.?WO 2008064345, 2008.
19. Baker, S. J.; Sanders, V; Akama, T.; Bellinger-Kawahara, C.; Freund, Y.; Kirk, M. R.; Plattner, J. J.; Zhang, Y. K.; Zhou, H.; Hernandez, V. S. “Boron-containing small molecules as anti-inflammatory agents.?WO 2007095638, 2007.
20. Baker, S. J.; Akama, T.; Alley, M. R. K.; Benkovic, S. J.; Dipierro, M.; Hernandez, V. S.; Hold, K. M.; Isaac, K.; Igor, L.; Mao, W.; Maples, K. R.; Plattner, J. J.; Rock, F.; Sanders, V.; Stemphoski, A. M.; Yiannikouros, G. P.; Zegar, S.; Zhang, Y. K.; Zhou, H. “Preparation of boron-containing small molecules and nucleosides for treating fungal infections.?WO 2007078340, 2007.
21. Baker, S. J.; Akama, T.; Alley, M. R. K.; Benkovic, S. J.; Dipierro, M.; Hernandez, V. S.; Hold, K. M.; Isaac, K.; Igor, L.; Mao, W.; Maples, K. R.; Plattner, J. J.; Rock, F.; Sanders, V.; Stemphoski, A. M.; Yiannikouros, G. P.; Zegar, S.; Zhang, Y. K.; Zhou, H. “Boron-containing small molecules which inhibit tRNA synthetase editing, their synthesis and use as antimicrobials.?US 2007 155699 A1 20070705 CAN 147:158454 AN 2007:733844, 2007.
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contact information
School of Pharmacy, Shanghai Jiao Tong University
800 Dongchuan Road, Shanghai, 200240
Office phone:+86 (21) 3420-6991
Lab. Phone: +86 (21) 3420-6373
Huchen Zhou hczhou@sjtu.edu,cn
Qingqing Meng qqmeng@sjtu.edu,cn
Current Graduate Students: Puhua Wu, Zhitao Qiao, Yaxue Zhao, Qing Wang, Jiong Zhang, Jin Du.
Previous Students (Current work): Long Ye (SJTU, School of Life Sciences and Biotechnology) Dazhong Ding (Shanghai Pharma Group), Mingxuan Wu (Princeton University, Department of Chemistry).
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More Information
Funded Projects:
National Natural Science Foundation of China, General Program (2008-2010)
Pujiang Talent Program, Science and Technology Commission of Shanghai Municipality (2007-2009)
Shuguang Scholar Award and Research Fund, Shanghai Municipal Education Commission (2008-2011)
NCET (New Century Excellent Talent) Fund, Education Ministry of China (2008)
Scientific Research Foundation for the Returned Overseas Chinese Scholars, Education Ministry of China (2008)
National Basic Research Program of China (973 Program), Ministry of Science and Technology of China, co-PI (2009-2013)
National Natural Science Foundation of China, Major Research Plan, co-PI (2009-2012)
International Collaborative Discovery Program (2007.04-2010.04)
