彩神v

导师风采

SUPERVISOR

李子刚 教授
职称:

教授,博士生导师,课题组长,北京大学“百人计划”特聘研究员,广东特支计划百千万工程领军人才,深圳市海外高层次人才

院系:

深圳研究生院化学生物学与生物技术学院

方向:

简介:

男,1978年3月生于安徽合肥,汉族。2001年于中国科学技术大学获学士学位,2004年于美国杜兰大学获硕士学位,2008年于芝加哥大学获得博士学位。 2009年起赴哈佛大学从事化学生物学研究。2010年至今独立开展稳定多肽二级结构的方法学研究、治疗性靶点研究、微生物毒力及抗感染治疗研究和多肽自组装材料研究等。

       李子刚教授19783月出生于安徽省合肥市,2001年于中国科学技术大学神经科学与生物物理学系取得学士学位,在周逸峰教授组从事Torch病毒感染儿童的弱视病理研究。2001年留学美国杜兰大学(Tulane University),师从合成化学家Chao-Jun Li教授,从事水相有机化学反应获得硕士学位;2004年开始在芝加哥大学(University of Chicago),师从Chuan He教授,从事化学生物学研究于2008年获得芝加哥大学研究生最高奖金Harper毕业论文奖(全校五人)并获得博士学位(Ph.D.)。2009年起赴哈佛大学(Harvard University)化学与化学生物学系师从Gregory Verdine教授作为美国国家癌症中心博士后奖金获得者(全美四人)从事化学生物学研究。2010年至今独立开展稳定多肽二级结构的方法学研究、治疗性靶点研究、微生物毒力及抗感染治疗研究和多肽自组装材料研究等。

奖项及荣誉

2017      拜耳学者奖
2016      广东特支计划百千万工程领军人才
2013      深圳市杰出青年基金奖
2012      深圳市海外高层次人才
2010      北京大学“百人计划”特聘研究员
2010      美国国家癌症中心博士后奖金  
2008      芝加哥大学Harper毕业论文奖

       我们的研究小组将在化学和生物交叉领域用化学方法解决生物学问题。我们的研究领域主要包括稳定多肽二级结构的方法学研究、治疗性靶点研究、微生物毒力及抗感染治疗研究和多肽自组装材料研究等四个方面。

1. 稳定多肽二级结构的方法学研究
       蛋白-蛋白相互作用 (PPIs) 通常被视为药物发现的非药物性靶点,大多数PPIs包括少于15个氨基酸残基的短螺旋多肽,通过化学手段将多肽稳定在某一固定构象的稳定多肽是重要的调节PPI的代表性化合物。我们课题组的相关研究关注多肽工程战略,致力于发展新型多肽螺旋构象稳定方法,以解释稳定多肽的二级构象对其生物物理性能的影响。与此同时我们通过化学稳定的多肽来研究重要蛋白靶点的生物功能和作用机制,为探索更加有效的药物前体奠定基础。

2. 治疗性靶点研究
       基于不同治疗性靶点的特征(ER-α, USP 30, Raf, LSD1, p53, HDAC1, IDE)设计和开发新的稳定多肽。

3. 微生物毒力及抗感染治疗研究
       我们课题组一个研究方向是关注人类重要病原微生物的毒力,利用结构生物学或计算化学手段及高通量药物筛选方法对小分子库进行筛选。针对人类病原体重要靶标蛋白开发一些小分子抑制剂用于抵抗病原微生物感染。

4. 多肽自组装材料研究
       生物纳米材料相比于许多无机材料更为环境友好。研究发现,许多短肽分子会自组装成规则有序的纳米结构,并常常会展现出许多独特的性质。我们课题组采用化学方法设计与合成具有特殊结构的短肽,开发更为便捷的组装体系,诱导和构建多肽纳米材料。在生物医药、可穿戴设备、植入设备以及可降解材料等领域具有广泛的应用前景

MEMBERS:

More details: http://web.pkusz.edu.cn/li/members/

SELECTED PUBLICATION

  1. 1. Kuan Hu,? Yixiang Jiang,? Wei Xiong, Hu Li, Pei-Yu Zhang, Feng Yin, Qianling Zhang, Hao Geng, Fan Jiang,* Zhou Li,* Xinwei Wang,* and Zigang Li* Science Advances, 2018,

  2. 2. DOI: 10.1126/sciadv.aar5907

  3. 3. Weihao Zheng, Xiaodan Cai, Shuiming Li and Zigang Li* “Autophosphorylation Mechanism of the Ser/Thr Kinase Stk1 From Staphylococcus aureus” Front. Microbiol., 2018

  4. 4. Xuan Qin,? Hui Zhao,? Yanhong Jiang, Feng Yin, Yuan Tian, Mingsheng, Xie, Xiyang Ye, Naihan Xu, Zigang Li* “Development of a potent peptide inhibitor of estrogen receptor α” Chinese Chemical Letters, 2018

  5. 5. Xiaodong Shi, Rongtong Zhao, Yixiang Jiang, Hui Zhao, Yuan Tian, Yanhong Jiang, Jingxu Li, Weirong Qin, Feng Yin*, Zigang Li* “Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation ” Chem. Sci., 2018, DOI: 10.1039/C7SC05109C

  6. 6. Wenjun Li,? Kuan Hu,? Qingzhou Zhang, Dongyuan Wang, Yue Ma, Zhanfeng Hou, Feng Yin*, Zigang Li* “N terminal N-methylation modulates chiral centre induced helical (CIH) peptides’ biophysical properties ” Chem. Commun. 2018; doi: DOI: 10.1039/C7CC09201F.

  7. 7. Yanhong Jiang,? Qiwen Deng,? Hui Zhao, Mingsheng Xie, Longjian Chen, Feng Yin, Xuan Qin, Weihao Zheng, Yongjuan Zhao* and Zigang Li* “Development of stabilized peptide-based PROTACs against estrogen receptor α” Acs Chemical Biology, 2017; doi: 10.1021/acschembio.7b00985

  8. 8. Xiaodan Cai,? Weihao Zhenga,? Shaokun Pan, Shengyuan Zhang, Youhua Xie, Haitao Guo, Guoxin Wang,? Zigang Li,? Ming Luo? “A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice” Antiviral Research, 2017

  9. 9. Mingsheng Xie, Hui Zhao, Qisong Liu, Yujia Zhu, Feng Yin, Yujie Liang, Yanhong Jiang, Dongyuan Wang, Kuan Hu, Xuan Qin, Zichen Wang, Yujie Wu, Naihan Xu, Xiyang Ye* , Tao Wang* , and Zigang Li* “Structural Basis of Inhibition of ERα-Coactivator Interaction by High-A?nity N Terminus Isoaspartic Acid Tethered Helical Peptides” J. Med. Chem., 2017; 60 (21),8731–8740

  10. 10. Kuan Hu,? Feng Yin,? Mengyin Yu, Chengjie Sun, Jingxu Li, Yujie Liang, Wenjun Li, Mingsheng Xie, Yuanzhi Lao, Wei Liang* , Zigang Li* “In-tether chiral center induced helical peptide modulators target p53-MDM2/MDMX and inhibit tumor growth in stem-like cancer cell” Theranostics, 2017; 7(18):4566-4576

  11. 11. Yuan Tian,? Xiangze Zeng, ?Jingxu Li, ?Yanhong Jiang, Hui Zhao, Dongyuan Wang, Xuhui Huang* and Zigang Li* “Achieving enhanced cell penetration of short conformationally constrained peptides through amphiphilicity tuning” Chemical Science, 2017

  12. 12. Yuan Tian, ? Yanhong Jiang, ? Jingxu Li, Dongyuan Wang, Hui Zhao, Zigang Li* “Effect of stapling architecture on physiochemical properties and cell permeability of stapled -helical peptides: a comparative study” ChemBioChem.2017; doi:10.1002/cbic.201700352

  13. 13. Jingxu Li, Kuan Hu, Hailing Chen, YuJie Wu, Longjian Chen, Feng Yin,* Yuan Tian,* and Zigang Li* “In-tether chiral center modulates the proapoptotic activity of KLA peptide” Chem. Commun. 2017;

  14. 14. Dan Yang,? Huasen Wang, ? Chengjie Sun, ? Hui Zhao, Kuan Hu, Weirong Qin, Rui Ma, Feng Yin, Xuan Qin, Qianling Zhang, Yongye Liang* and Zigang Li* “Development of a high quantum yield dye for tumour imaging” Chemical Science, 2017; doi: 10.1039/c7sc02698f

  15. 15. Hui Zhao, ? Xuan Qin, ? Dan Yang, ? Yanhong Jiang, Weihao Zheng, Dongyuan Wang, Yuan Tian, Qisong Liu, Naihan Xu* and Zigang Li* “The development of activatable lytic peptides for targeting triple negative breast cancer” Cell Death Discovery,2017; doi:10.1038/cddiscovery.2017.37

  16. 16. Xiaodong Shi, ? Yixiang Jiang, ? Dan Yang, Hui Zhao, Yuan Tian, Zigang Li* “Reversibly switching the conformation of short peptide through in-tether chiral sulfonium auxiliary” Chinese Chemical Letters, 2017; doi:10.1016/j.cclet.2017.07.003

  17. 17. Feng Yin, ? Kuan Hu, ? Si Chen,? Dongyuan Wang, Jianing Zhang, Mingsheng Xie, Dan Yang, Meng Qiu, Han Zhang* and Zi-gang Li*a “Black phosphorus quantum dot based novel siRNA delivery systems in human pluripotent teratoma PA-1 cells”  J. Mater. Chem. B, 2017; doi:10.1039/c7tb01068k

  18. 18. Kuan Hu,?, Chengjie Sun,?, Zigang Li,* “Reversible and versatile on-tether modification of chiral center-induced helical peptides”  Bioconjugate Chem. 2017; doi:10.1021/acs.bioconjchem.7b00321 

  19. 19. Kuan Hu,? Chengjie Sun,? Dan Yang,? Yujie Wu, Chuan Shi, Longjian Chen, Tao Liao, Jialin Guo, Yinghuan Liu and Zigang Li* “A precisely positioned chiral center in an i, i +7 tether modulates the helicity of the backbone peptide” Chem. Commun. 2017; doi: 10.1039/c7cc03799f

  20. 20. Kuan Hu,? Chengjie Sun,? Mengying Yu, Wenjun Li, Huacan Lin, Jialin Guo, Yixiang Jiang, Chengxiang Lei, and Zigang Li* “Dual in-tether chiral centers modulate peptide helicity” Bioconjugate Chem. 2017; doi: 10.1021/acs.bioconjchem.7b00171 

  21. 21. Yanhong Jiang, Hui Zhao, Yuan Tian, Zigang Li* “Lipid–cell-penetrating-peptide conjugates as effective delivery systems” Synlett2017; doi:10.1055/s-0036-1588807

  22. 22. Dongyuan Wang, Xuan Qin, Hui Zhao, Zigang Li* “N-Cap helix nucleation: methods and their applications ”Sci. CHINA Chem. , 2017 ; doi:10.1007/s11426-016-9033-y                                                  

  23. 23. Yuan Tian,? Dan Yang,? Xiyang Ye and Zigang Li* “Thioether-derived macrocycle for peptide secondary structure fixation” Chem. Rec. , 2017;17,1–13. doi:10.1002/tcr.201600137

  24. 24. Feng Yin,? Kuan Hu,? Yangzi Chen, Mengying Yu, Dongyuan Wang, Qianqian Wang, Ken-Tye Yong, Fei Lu, Yongye Liang , Zigang Li*SiRNA delivery with PEGylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer” Theranostics, 2017; 7(5):1133-1148. doi:10.7150/thno.17841

  25. 25. Hui Zhao, Yanhong Jiang, Yuan Tian, Dan Yang, Xuan Qin and Zigang Li* “Improving cell penetration of helical peptides stabilized by N-terminal crosslinked aspartic acids” Organic & Biomolecular Chemistry,2016, DOI: 10.1039/c6ob02501c

  26. 26. Yixiang Jiang, Kuan Hu, Xiaodong Shi, Qingzhuang Tang, ZiChen Wang, Xiyang Ye* and Zigang Li* “Switching substitution groups on the in-tether chiral centre in?uences backbone peptides permeability and target binding a?nity Organic & Biomolecular Chemistry,2016, DOI: 10.1039/c6ob02289h

  27. 27. Qingzhou Zhang, Fan Jiang, Bingchuan Zhao, Huacan Lin, Yuan Tian, Mingsheng Xie, Guoyun Bai, Adam M. Gilbert, Gilles H. Goetz, Spiros Liras, Alan A. Mathiowetz, David A. Price, Kun Song, Meihua Tu, Yujie Wu, Tao Wang,*, Mark E. Flanagan,*,  Yun-Dong Wu* & Zigang Li* “Chiral sulfoxide-induced single turn peptide α-helicity ” Scientific Reports, 2016, DOI:10.1038/srep38573

  28. 28. Jingxu Li, Yuan Tian, Dongyuan Wang, Yujie Wu, Xiyang Ye*, Zigang Li* “An in-tether sulfoxide chiral center influences the biophysical properties of the N-capped peptides” Bioorganic & Medicinal Chemistry, 2016, DOI: http://dx.doi.org/10.1016/j.bmc.2016.11.042

  29. 29. Kuan Hu,? Wenjun Li,? Mengying Yu, Chengjie Sun, and Zigang Li* “Investigation of cellular uptakes of the in-tether chiral-center-induced helical pentapeptides”  Bioconjugate Chem, 2016, DOI: 10.1021/acs.bioconjchem.6b00492 

  30. 30. Tao Liao,? Fang Yuan,? Chuan Shi, Chuan-Xin He* and Zigang Li* “Lanthanide chelate-encapsulated polystyrene nanoparticles for rapid and quantitative immunochromatographic assay of procalcitonin” RSC Advances, 2016, 6, 103463, DOI: 10.1039/c6ra23816e

  31. 31. Huacan Lin, Yixiang Jiang, Kuan Hu, Qingzhou Zhang, Chuanxin He*, Tao Wang* and Zigang Li*  “An in-tether sulfilimine chiral center induces β-turn conformation in short peptides” Organic & Biomolecular Chemistry, 2016, DOI: 10.1039/C6OB01805

  32. 32. Hui Zhao?, Qi-Song Liu?, Hao Geng?, Yuan Tian, Min Cheng, Yan-Hong Jiang, MingSheng Xie, Xiao-Gang Niu, Fan Jiang, Ya-Ou Zhang, Yuan-Zhi Lao, Yun-Dong Wu,* NaiHan Xu,* and Zi-Gang Li* “Crosslinked aspartic acids as helix-nucleating templates” Angew. Chem.Int. Ed.2016 DOI: 10.1002/ange.201606833

  33. 33. Weihao Zheng, Xiaodan Cai, Mingsheng Xie,Yujie Liang, Tao Wang* and Zigang Li*”Structure-based-identification of a potent inhibitor targeting stp1-mediated virulence regulation in staphylococcus aureus” Cell Chemical Biology, 2016, http://dx.doi.org/10.1016/j.chembiol.2016.06.014

  34. 34. Huacan Lin, Yixiang Jiang, Qingzhou Zhang, Kuan Hu and Zigang Li* “An in-tether sulfilimine chiral center induces helicity in short peptides” Chem. Commun. 2016 DOI: 10.1039/C6CC04508A

  35. 35. Bingchuan Zhao, Qingzhou Zhang and Zigang Li* “Constructing thioether-tethered cyclic
    peptides via on-resin intra-molecular thiol–ene reaction”  Journal of Peptide Science. 2016 DOI : 10.1002/psc.2902

  36. 36. Yuan Tian,? Dongyuan Wang,?  Jingxu Li, Chuan Shi, Hui Zhao, Xiaogang Niu and Zigang Li* “A proline-derived transannular N-cap for  nucleation of short a-helical peptides” ChemComm. 2016 DOI: 10.1039/c6cc04672j

  37. 37. Bingchuan Zhao,? Dan Yang,? Jack Ho Wong, Jianpeng Wang, Cuiming Yin, Yuxia Zhu, Shangrong Fan*, Tzi Bun Ng*, Jiang Xia* and  Zigang Li* “A Thioether-Stabilized d-Proline–l-Proline-Induced β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability” ChemBioChem. 2016 DOI: 10.1002/cbic.201600179

  38. 38. F. Yuan, Y. Deng, W. Zhou, M. Zhang, Z. Li.* “A simple and novel method for the quantitative detection of 5-hydroxymethylcytosine using carbon nanotube field- effect transistors”, Nano Res. 2016, 9, 1701-1708

  39. 39. Y. Deng,? F. Yuan,? W. Zhou, M. Zhang, Z. Li. ” Highly uniform DNA biosensors based on threshold voltage of carbon nanotube thin-film transistors “, Nano. 2016, 11, 1650060.

  40. 40. T. Liao,? F. Yuan,? H. Yu and Z. Li.* “A ultrasensitive ELISA method for detection of procalcitonin based on magnetic beads and enzyme-antibody labeled gold nanoparticles”, Anal. Methods. 2016, 8, 1577-1585.

  41. 41. Y. Wang, Z. Xia, S. Du, F. Yuan, Z. Li, Z. Li, Q. Dai, H. Wang, S. Lou, S. Zhang, H. Zhou. ” Solution-processed photodetectors based on organic-inorganic hybrid perovskite and nanocrystalline graphite “, Nanotechnology. 2016, 27, 175201

  42. 42. Kuan Hu, Hao Geng, Qingzhou Zhang, Qisong Liu, Mingsheng Xie, Chengjie Sun, Wenjun Li,Huacan Lin, Fan Jiang, Tao Wang,* Yun-Dong Wu,* and Zigang Li*  An In-tether Chiral Center Modulates the Helicity, Cell Permeability,and Target Binding Affinity of a Peptide. Angew. Chem. Int. Ed. 2016DOI: 10.1002/anie.201602806R1.

  43. 43. Yuan Tian, Jingxu Li, Hui Zhao, Xiangze Zeng, Dongyuan Wang, Qisong Liu, Xiaogang Niu, Xuhui Huang, Naihan Xu* and Zigang Li* Stapling of unprotected helical peptides via photoinduced intramolecular thiol–yne hydrothiolation? Chem. Sci., 2016, Advance Article.

  44. 44. Q Liu, H Zhao, Y Jiang, M Wu, Yuan Tian, D Wang, Y Lao, N Xu* & Z Li* Development of a lytic peptide derived from BH3-only proteins. Cell Death Discovery (2016) 2, 16008;

  45. 45. Bingchuan Zhao, Huacan Lin, Dan Yang, Xiyang Ye* and Zigang Li* Disulfide Bridges in Defesins  Curr.Top.Med.Chem.2015;16(2):206-19.

  46. 46. Yujie Wang, Hong Zhang, Qingzhou Zhang, Yujie Liang, Lin Ma, Hongsheng Tan, Yuanzhi Lao,* Hongxi Xu* and Zigang Li*  Genetically encoded fluorescence screening probe for MgrA, a global regulator in Staphylococcus aureus?   RSC Adv., 2015, 5, 87216–87220.

  47. 47. Zhao, W. 1; Qian, H. 1; Li, Z.*; Sun, J.* (1: equal contribution) Catalytic Ring Expansion of Cyclic Hemiaminals for the Synthesis of Medium Ring Lactams.
    Angew. Chem., Int. Ed. 2015, 54, 10143-10146.

  48. 48. Weihao Zheng, Yujie Liang, Hui Zhao, Jianing Zhang,  Zigang Li*., 5,5′-Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1., ChemBioChem., 2015, 16, 1035-1040.

  49. 49. Qisong Liu, Fang Yuan, YuJie Liang, Zigang Li*., Cadmium adsorption by E. coli with surface displayed CadR., RSC Adv., 2015, 5, 16089-16092.

  50. 50. Qingzhou Zhang, Yuan Tian, Yuanzhi lao, Zigang Li*., Peptides-Staple Method Development and Its Application in Cancer Therapy., Curr. Med. Chem., 2014, 21, 2438-2452.

  51. 51. Qingzhou Zhang, Xiaodong Shi, Yanhong Jiang, Zigang Li*., Influence of α-methylation in constructing stapled peptides with olefin metathesis., Tetrahedron., 2014, 42, 7621-7626.

  52. 52. Wenbo Sun, Huacan Lin, Wenyu Zhou* and Zigang Li*., Oxidative ortho-amino-methylation of phenols via C-H and C-C bond cleavage., RSC Adv., 2014, 4, 7491-7494.

  53. 53. Lianbo Li, Weili Zhang, Qisong Liu, Yu Gao, Ying Gao, Yun Wang, David Zhigang Wang, Zigang Li and Tao Wang*., Structural Insights on the Bacteriolytic and Self-protection Mechanism of Muramidase Effector Tse3 in Pseudomonas aeruginosa., J. Bio. Chem., 2013, published online.

  54. 54. Bing-Chuan Zhao, Qing-Zhou Zhang, Wen-Yu Zhou, Hu-Chun Tao* and Zi-Gang Li*., Silver catalyzed synthesis of 4-trifluoromethyl substituted quinolines in water., RSC Adv., 2013, 3, 13106-13109

  55. 55. Wanxiang Zhao, Zigang Li*, and Jianwei Sun *., A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones without High Dilution or Slow Addition., J. Am. Chem. Soc., 2013, 135 (12), 4680–4683

  56. 56. Shunyou Cai, Xinyang Zhao, Xinbo Wang, Qisong Liu, Prof.?Dr. Zigang Li*, Prof.?Dr. David Zhigang Wang*., Visible-Light-Promoted C-C Bond Cleavage: Photocatalytic Generation of Iminium Ions and Amino Radicals, Angew. Chem. 2012,51(32), 8050-8053

  57. 57. Yu-Ming Zhao, Yik Tam, Yu-Jie Wang, Zigang Li, and Jianwei Sun*., N-Heterocyclic Carbene-Catalyzed Internal Redox Reaction of Alkynals: An Efficient Synthesis of Allenoates, Org. Lett. 2012, 14(6), 1398-1401

  58. 58. Fei Sun, Lu Zhou, Bing-Chuan Zhao, Xin Deng, Hoonsik Cho, Chengqi Yi, Xing Jian, Chun-Xiao Song, Chi-Hao Luan, Taeok Bae, Zigang Li*and Chuan He*. Targeting MgrA-Mediated Virulence Regulation in Staphylococcus aureus., Chemistry & Biology 2011,18, 1032-1041

地址:北京大学新太阳学生中心5楼

咨询电话:010-62751354 监督电话:010-62756913

Copyright ? 2003-2018 彩神v

相关链接:

本站二维码