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.

II. Medicinal Chemistry of Natural Products

We are interested in the total synthesis of bioactive natural products and studies on their medicinal chemistry. We have completed the total synthesis of several antibiotics and we are engaging their medicinal chemistry now towards the development of next-generation antibiotics.

III. Function Definition of Macromolecules and their PTMs

Glycosylation, 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.

IV. Drug Development

Phage display is one of the most powerful techniques for drug discovery. Coupled with the advantages of synthetic chemistry (new chemistry reaction, synthetic protein with PTM of interested, mirror image proteins etc. ), we hope to expand our library for drug development.

I. NEW Methods developed in our lab

1) Scheme of Ser/Thr Ligation (STL) (Proc. Natl. Acad. Sci. USA, 2013)

2) P B Desulfurization: An Enabling Method for Protein Chemical Synthesis and Site-Specific Deuteration (Angewandte Chemie International Edition, 2017)

3) PT ligation for native protein modification (Org. Lett. 2016)

4) Scheme of Ring-Closing Glycosylation (RCG) (J. Org. Chem. 2014)

To synthesize carbohydrates, a methodology developed in the lab is the ring-closing glycosylation via nonglycosylating pathway

5) A Solution to Chemical Pseudaminylation via a Bimodal Glycosyl Donor for Highly Stereocontrolled α- and β-Glycosylation. (Org. Lett. 2019)

6) Chemoselective Peptide Cyclization and Bicyclization Directly on Unprotected Peptides (J. Am. Chem. Soc. 2019)

7) Cysteine/Penicillamine ligation independent of terminal steric demands for protein chemical synthesis (CPL). (Angew. Chem. Int. Ed. 2020)

II. Medicinal Chemistry of Natural Products

1)Total Synthesis of Pseudomonas aeruginosa 1244 Pilin Glycan ( J. Am. Chem. Soc. 2017)

2) Total synthesis of teixobactin (Nature Communications. 2016)

3) Total synthesis of daptomycin (J. Am. Chem. Soc. 2013)

4) Total synthesis of Antibiotics A54145 (Org. Lett. 2019)

5) Total synthesis of Malacidin A (Angew. Chem. Int. Ed. 2020)