Our research interest is to design methods for the genetic incorporation of noncanonical amino acids into proteins in living cells and apply these methods in three major directions: deciphering functions of protein posttranslational modifications, small molecule sensing, and expanding chemical diversities of phage display libraries. To study protein posttranslational modifications, we have constructed methods for the site-specific installation of lysine acetylation and methylation in proteins and will apply them to study functional roles of these two modifications on p53, a tumor suppressor protein. We have also developed a strategy to site-specifically install two noncanonical amino acids into one protein in E. coli and are applying this approach to construct biosensors for small organic molecules and metal ions. Phage display is an efficient method to identify peptides for therapeutic interventions. However, a phage display peptide library has limited structure motifs and functional groups because only 20 natural amino acids can be used to generate a library. We plan to expand the chemical diversity of a phage display library by incorporating multiple noncanonical amino acids and chemically modifying them to extend functional diversities. Screening this unnatural phage display library against therapeutic targets such as c-Abl tyrosine kinase is expected to identify highly potent inhibitors.
- Li, J., Yuan, S., Qin, J., Pang, J., Zhang, P., Zhang, Y., ... Zhou, H. (2020). Stepwise Assembly of Turn‐on Fluorescence Sensors in Multicomponent Metal–Organic Frameworks for in Vitro Cyanide Detection. Angewandte Chemie - International Edition. 59(24), 9319-9323.
- Tharp, J. M., Hampton, J. T., Reed, C. A., Ehnbom, A., Chen, P., Morse, J. S., ... Liu, W. R. (2020). An amber obligate active site-directed ligand evolution technique for phage display.. Nature Communications. 11(1), 1392.
- Qiao, Y., Yu, G. e., Kratch, K. C., Wang, X. A., Wang, W. W., Leeuwon, S. Z., ... Liu, W. R. (2020). Expressed Protein Ligation without Intein.. Journal of the American Chemical Society.
- Morse, J. S., Lalonde, T., Xu, S., & Liu, W. R. (2020). Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV.. Chembiochem : a European journal of chemical biology.
- Wang, W. W., Angulo-Ibanez, M., Lyu, J., Kurra, Y., Tong, Z., Wu, B. o., ... Liu, W. R. (2019). A Click Chemistry Approach Reveals the Chromatin-Dependent Histone H3K36 Deacylase Nature of SIRT7.. Journal of the American Chemical Society.
- Wang, Xiaoshan (2018-05). The Nitrilimine-Alkene Cycloaddition Mechanism and Phage-displayed Cyclic Peptide Libraries for Drug Discovery. (Doctoral Dissertation)
- Wang, Zhipeng (2018-05). The Chemical Synthetic Investigation of Proteins with Sitespecific Lysine Post-Translational Modifications. (Doctoral Dissertation)
- Sharma, Vangmayee (2017-08). The Engineering and Optimization of Pyrrolysyl-Synthetase as a Tool for Noncanonical Amino Acid Incorporation. (Doctoral Dissertation)
- Hsu, Willie Weili (2017-08). The Investigation of Sirtuin Activities on Short-Chained Mono-Acylated Histone H3 Tetramers and Nucleosomes. (Doctoral Dissertation)
- Deonarine-Chihak, Sasha Mala (2016-12). A Tetrazine-Terminal Alkene System for Profiling Protein Fatty Acylation Modifications. (Master's Thesis)