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个人介绍

教学工作

本科生:《药物化学》

研究领域

以感染性疾病和肿瘤为重点、以分子识别为基础的小分子设计合成及其用于生物体系的功能调节和生物机理的揭示。(有机合成;计算机辅助药物设计;化学生物学)

本课题组从生物体系中需要解决的关键问题出发,以化学小分子与生物大分子的相互作用能够调控生命活动为原则,设计并合成小分子化合物,选择性地作用于生物体系,进而通过信号转导通路的反馈理解其作用机制。并由此引导新化合物的定向设计和合成,最终达到有目的地对生命活动进行调控。

从分子水平上来说,蛋白质-蛋白质相互作用和配体-蛋白质相互作用在生命活动的调控过程中起关键作用。我们以在重大疾病发生发展中有重要作用的蛋白质-蛋白质和配体-蛋白质相互作用作为研究对象, 运用分子模拟 (Maestro软件包, Schrodinger Inc.) 和有机合成的手段设计并合成能够干扰上述生物过程的小分子化合物。再通过细胞分子生物学手段得到它们在细胞信号转导中的作用和机制。在生物机制研究产生突破的反馈下进一步扩展化学研究的深度和广度。最终以发现重大疾病的生物机制,发现新的药物靶标和新型药物分子为目的。

目前研究包括:(1)抗感染和抗肿瘤化合物的发现;(2)用于揭示生物机制的小分子探针的设计、合成及其生物作用机理的研究。主要包括半胱氨酸蛋白酶抑制剂和氨酰tRNA合成酶抑制剂作为抗感染化合物的研究,以及新型生物作用机制和新靶标的化学生物学研究。


项目

  1. 国家自然科学基金优秀青年基金.

  2. 国家重大科学研究计划(973),学术骨干(2012-2016).

  3. 国家自然科学基金重大研究计划重点项目,参与(2009-2012).

  4. 国家自然科学基金青年基金(2008-2010).

  5. 上海科委浦江人才计划(2007-2009).

  6. 上海教委曙光学者支持计划(2008-2011).

  7. 教育部新世纪优秀人才支持计划(2008).

  8. 国际合作项目 (2007-2010).


代表成果

1.Liu, C.; 1 Yin, Q.;1 Zhou, H.;1 Wu, Y.; Pu, J. ; Xia, L.; Liu, W.; Huang, X.; Jiang, T.; Wu, M.; He, L.; Zhao, Y.; Wang, X.; Xiao, W.; Chen, H.; Zhao, Q.; Zhou, A.; Wang, L.; Sun, H.; Chen, G. “Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells.” Nature Chem. Biol. 2012, 8, 486-493. 

2.Qiao, Z.; Wang, Q.; Zhang, F.; Wang, Z.; Bowling, T.; Nare, B.; Jacobs, R. T.; Zhang, J.; Ding, D.; Liu, Y.; Zhou, H.* “Chalcone-benzoxaborole hybrid molecules as potent antitrypanosomal agents.” J. Med. Chem. 2012, 55, 3553-3557. 

3.Zhao, Y.; Wang, Q.; Meng, Q.; Ding, D.; Yang, H.; Gao, G.; Li, D.; Zhu, W.; Zhou, H.* “Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis.” Bioorg. Med. Chem. 2012, 20, 1240-1250. 

4.Zhang, Y.; Plattner, J.; Freund, Y.; Easom, E.; Zhou, Y.; Ye, L.; Zhou, H.; Waterson, D.; Gamo, F.; Sanz, L.; Ge, M.; Li, Z.; Li, L.; Wang, H.; Cui, H. “Benzoxaborole antimalarial agents. 2. Discovery of fluoro-substituted 7-(2-carbozyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles.” Bioorg. Med. Chem. Lett. 2012, 22, 1299-1307.

5.Wu, M.; Meng, Q, Ge, M.; Bai, L.; Zhou, H.* “2,3,6-Trideoxy sugar nucleotides: synthesis and stability.” Tetrahedron Lett. 2011, 52, 5799-5801. 

6.Qiao, Z.; Wang, W.; Wang, L.; Wen, D.; Zhao, Y.; Wang, Q.; Meng, Q.; Chen, G.; Wu, Y.; Zhou, H.* “Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors.” Bioorg. Med. Chem. Lett.2011, 21, 6389-6392.

7.Wu, P.; Meng, Q.; Zhou, H. * “Synthesis of a novel pyrrolo-benzoxaborole scaffold and its derivatization via Friedel–Crafts reaction catalyzed by anhydrous stannic chloride.” Chin. Chem. Lett. 2011, 22, 1411-1414. 

8.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, 54, 1276-1287.

 9.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. 

10.Wu, Y.; Zhou, H.; Chen, G “Molecular mechanisms of leukemia-associated protein degradation.” Front. Med. China2010, 4, 363-370. 

11.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. 

12.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. 

13.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. 

14.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. 

15.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. 

16.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. 

17.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.

18.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. 

19.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.

20.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. 

21.Zhou, H. and Hamilton, A. D. “Protein surface recognition.”, in “Encyclopedia of Supramolecular Chemistry”, Taylor & Francis, 2006, 1: 1, 1-13. 

22.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. 

23.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. 

24.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. 

25.Akama, T.; Baker, S. J.; Hernandez, V. S.; Plattner, J. J.; Zhang, Y. K.; Zhou, H.; “Microorganism killing compounds.” WO 2008064345, 2008.

26.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. 

27.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. 

28.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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