个人简介
2018年3月-至今:香港大学化学系,教授
2014年7月-2018年2月: 香港大学,副教授(提前终身教授)
2009年7月-2014年6月: 香港大学,助理教授
2007年2月-2009年6月: 斯隆 - 凯特琳癌症中心/哥伦比亚大学,博士后
2003年7月-2006年12月:哈佛大学,博士,美国
2000年8月-2003年6月:阿尔伯塔大学,硕士,加拿大
1995年9月-1999年6月:南开大学,学士
研究领域
开展多肽分子库及其药物化学的研究
I. Method developing for Bio-macromolecules synthesis
Chemical tools have allowed for many biological question to be answered at a molecular level. One long-term goal of this research program is to design and discover chemical methods enabling chemical synthesis of bio-macromolecules, including proteins, carbohydrates, and proteins with post-translational modifications. We are also engaged to development of fluorogenic reagents for labeling proteins and carbohydrates and sensors for detecting bio-molecules under physiological conditions.
One of innovative methods grown from this laboratory is Serine/Threonine Ligation (STL), which is allowing us to chemically synthesize proteins. Besides, an enabling method for protein chemical synthesis and site-specific deuteration was developed recently: P B Desulfurization. PT ligation also is a powerful reaction for native protein modification.
II. Medicinal Chemistry of Natural Products
We are interested in the total synthesis of bioactive natural products and studies on their medicinal chemistry. Recently, we have completed the total synthesis of daptomycin – an antibiotic approved by the FDA in 2003 and teixobactin, and we are engaging their medicinal chemistry now towards the development of next-generation antibiotics.
III. Function definition of Macromolecules and their PTMs
Phosphorylation, methylation, acetylation and other post-translation modifications can be easily achieved at specific site by synthetic chemistry, which is still diffcult via protein expression. So,we take advantage of organic synthesis and have established well-equipped biological laboratory for functional research of macromolecules. Also, we are interested in defining targets of natural products in cells. Combining chemical cross linking, click chemistry and metabolic labeling, we expect to identify their targets for therapy improvement.
近期论文
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1. Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation. Lam, H. Y.; Zhang, Y.; Liu, H.; Xu, J.; Wong, C. T.; Li, X.* J. Am. Chem. Soc. 2013, 135, 6272.
2. Protein chemical synthesis by serine and threonine ligation. Zhang, Y.; Xu, C.; Lam, H. Y.; Lee, C. L; Li, X.* Proc. Natl. Acad. Sci. USA, 2013, 110, 6657.
3. Synthesis of constrained head-to-tail cyclic tetrapeptides by an imine-induced ringclosing/contraction strategy. Wong, C. T. T.; Lam, H. Y.; Song, T.; Chen, G.*; Li, X.* Angew.Chem. Int. Ed. 2013, 52, 10212.
4. Enabling N-to-C Ser/Thr Ligation for Convergent Protein Synthesis via Combining Chemical Ligation Approaches Lee, C. L.; Liu, H.; Wong, C. T. T.; Chow, H. Y.; Li, X.*. J. Am. Chem. Soc.2016, 138, 10477.
5. Jin, K.; Sam, I . H.; Po, K. H. L.; Lin, D.; Ghazvini Zadeh, E. H.; Chen, S.*; Yuan, Y*.; Li, X.*Total synthesis of teixobactin. Nat. Commun. 2016, 7, 12394.
6. Total Synthesis of Pseudomonas aeruginosa 1244 Pilin Glycan via de Novo Synthesis of Pseudaminic Acid. Liu, H.; Zhang, Y.; Wei, R.; Andolina, G.; Li, X.* J. Am. Chem. Soc. 2017, 139,13420. (selected as the Cover).
7. P-B desulfurization: an enabling method for protein chemical synthesis and site-specific deuteration. Jin, K.; Li, T.; Chow, H. Y.; Liu, H.; Li, X.* Angew. Chem. Int. Ed. 2017, 56, 14607.(VIP paper).
8. Metabolic Labeling of Pseudaminic Acid-Containing Glycans on Bacterial Surfaces. Andolina, G.; Wei, R.; Liu, H.; Zhang, Q.; Yang, X.; Cao, H.; Chen. S.; Yan, A.; Li, X. D.; Li, X.* ACS Chem.Biol. 2018, 13, 3030.
9. Serine/Threonine Ligation: Origin, Mechanistic Aspects and Applications. Liu, H.; Li, X.* Acc.Chem. Res. 2018, 51, 1643.
10. Intrinsic cleavage of RNA polymerase II adopts a nucleobase-independent mechanism assisted by transcript phosphate. Tse, C. K.; Xu, J.; Xu, L.; Sheong, F. K.; Wang, S.; Chow, H.Y.; Gao, X.; Li, X.; Cheng, P. P. H.; Wang, D.; Zhang, Y.; Huang, X. Nature Catalysis, 2019, 2,228.