Using synthetic organic chemistry and molecular biology as major tools to study and manipulate biologically important enzymes/proteins. Currently, I have four projects in my lab.
1. Studies of ghrelin acylation by ghrelin O-acyltransferse (GOAT).
GOAT was recently discovered1-2 as a potential drug target for curing obesity. We will investigate its molecular mechanisms and design effective inhibitors to it.
2. Mechanistic studies of polyhydroxyalkanoate (PHA) biosynthesis.
Biodegradable plastic PHAs can substitute oil-based plastics that are non-biodegradable. Our ultimate goal is to understand mechanisms of proteins involved in PHA biosynthesis and to engineer them to produce PHAs in an economically competitive fashion, which will help to protect our environment and save energy.
3. Investigation of peptidoglycan glycosyl-transferases (PGTs) in peptidoglycan biosynthesis.
PGT catalyze the final step of polymerizing Lipid II to form the nascent bacterial wall. Because their function is unique and essential for bacterial survival, PGTs have been the major target of clinically used antibiotics. Our goals are to understand the mechanism of substrate recognition by PGTs, to develop a model that can predict interactions between PGTs and substrate, and to design novel inhibitors to PGTs.
4. Site-specific protein labeling using SNAP tag.
Selective labeling of proteins has become an essential tool to visualize and characterize biological activities inside living cells. The SNAP tag was first introduced by Kai Johnsson using a human O6-alkylguanine-DNA alkyltransferase (hAGT), which transfers the alkyl group from its substrate, O6-alkylguanine-DNA to one of its cysteine residues. Our goals are to develop novel small molecule probes for specific labeling and apply this technology for detection of protein-protein interactions.
1. Zhang, W., Chen, C., Cao, R., Maurmann, L., and Li, P. "Inhibitors to polyhydroxyalkanoate (PHA) synthases: synthesis, molecular docking, and implications" Chembiochem 2014, in press.
2. Zhang, W., Shrestha, R., Buckley, R. M., Jewell, J., Bossmann, S. H., Stubbe, J., and Li, P. "Mechanistic insight with HBCH2CoA as a probe to polyhydroxybutyrate (PHB) synthases" ACS Chem. Biol. 2014, 9, 1773-1779.
3. Li, P.; Chakraborty, S and Stubbe, J. “Detection of Covalent and Non-covalent Intermediates in the Polymerization Reaction Catalyzed by a C149S Class III Polyhydroxybutyrate Synthase.” Biochemistry, 2009, 9202-9211.
4. Li, P.; Sergueeva, Z. A. and Shaw, B. R. “Nucleoside and Oligonucleoside Boranophosphates: Chemistry and Properties.” Chem. Rev. 2007, 4746-4796.
5. Li, P.; Xu, Z.; Liu, H. Y.; Wennefors, C. K.; Dobrikov, M.; Ludwig, J.; Shaw, B. R. “Synthesis of a-P-Modified Nucleoside Diphosphates with Ethylenediamine.” J. Am. Chem. Soc. 2005, 16782-16783.
6. Li, P. and Shaw, B. R. “Synthesis of Nucleoside Boranophosphoramidate Prodrugs Conjugated with Amino Acids.” J. Org. Chem. 2005, 70, 2171-2183.
7. Li, P. and Shaw, B. R. “Convenient Synthesis of Nucleoside Borane Diphosphate Analogues: Deoxy- and Ribonucleoside 5’-Pa-Boranodiphosphates” J. Org. Chem. 2004, 69, 7051-7057.
8. Shen, Y. C. and Li, P. “Stereoselective Synthesis of Trifluoromethylated Vinyl- and Dienylphosphonates with g-Alkoxycarbonyl Moiety” J. Fluorine Chem. 2004, 125, 63-66.
9. Li, P.; Dobrikov, M.; Liu, H. Y. and Shaw, B. R. “Synthesis and Substrate Properties of Acyclothymidine Triphosphate and a-P-Boranotriphosphate for Retroviral Reverse Transcriptase.” Org. Lett. 2003, 5, 2401-2403.
10. Li, P. and Shaw, B. R. “Synthesis of Nucleoside 3¢,5¢-Cyclic Boranophosphorothioates – A New Type of Cyclic Nucleotides.” Chem. Commun. 2002, 2890-2891.
11. Li, P. and Shaw, B. R. “Synthesis of Prodrug Candidates: Conjugates of Amino Acid with Nucleoside Boranophosphate.” Org. Lett. 2002, 4, 2009-2012.
12. Shen, Y. C.; Li, P.; Ni, J. H. and Sun, J. “A Novel Double Olefination. Highly Stereoselective Synthesis of Trifluoromethylated 1,3-Butadienylphosphonates.” J. Org. Chem. 1998, 63, 9396-9398.