Bingchen Yu
Assistant Professor Chemistry- Education
B.S., 2014 Shandong University,
Ph.D., 2018 Georgia State University
Postdoc, 2019 Georgia State University
Postdoc, 2023 University of California, San Francisco
Assistant Professor, 2023 Georgia State University
- Specializations
Chemical biology, organic chemistry, medicinal chemistry, molecular biology, drug delivery, genetic code expansion
- Biography
The Yu lab at GSU is dedicated to developing innovative chemical tools to study signal transduction and medicine in the context of protein-biomolecule interactions. Proteins interact with proteins, carbohydrates, nucleic acids, and lipids. These interactions govern every aspect of life. Deciphering these interactions can contribute to the understanding of the fundamental aspects of life and open up diverse opportunities for therapeutic intervention.Despite the critical roles of protein-biomolecule interactions, the lack of enabling tools greatly hindered the efforts to study such interactions and leverage these interactions for therapeutic purposes. The current methods of capturing protein-biomolecule interactions such as affinity purification-mass spectrometry relies on the reversible interaction, which often leads to large variation, false positive signals, and cannot distinguish direct from indirect interactors. To address these challenges, our lab will leverage our expertise in organic synthesis, molecular biology, and protein science to covalently capture these interactions for mechanistic studies and therapeutic developments.
- Mapping protein-biomolecule interactions via protein engineering.
This strategy genetically incorporates a latent bioreactive unnatural amino acid (Uaa), into a protein of interest. The latent Uaa itself has low activity, avoiding non-specific interactions. However, upon protein-target binding, the close contact would trigger the cross-linking reaction between the latent Uaa and the nucleophiles on the target. These proximity-enabled chemical reactions can irreversibly cross-linking the interacting protein-biomolecule. Subsequent mass spectrometry analysis would reveal the interacting biomolecules in high specificity. The proximity-enabled chemistry used in our lab includes sulfur(VI) fluoride exchange (SuFEx) and phosphorus fluoride exchange (PFEx). Additionally, we use photo-activated cross-linkers such as aryl azides and diazirines as complementary strategies for the proximity-enabled chemical cross-linkers.
Currently, we are focusing on probing protein post-translational modification (PTM)-mediated protein-protein interactions (PPIs) and identify new PPIs as therapeutic targets.
- Probing protein-biomolecule interactions via covalent small molecule probes.
Besides protein engineering, we are developing covalent small molecule probes to study signal transduction and facilitate drug discovery. Harvesting the power of organic synthesis and medicinal chemistry, we can install versatile chemical functional groups into small molecules of interest and investigate the targets and biological significance of such molecules.
- Small molecule drug discovery targeting challenging targets.
There is a growing number of disease-related targets that have been discovered but deemed “undruggable.” These targets typically have flat surfaces without well-defined grooves or pockets for binding, making therapeutic development challenging. To address these challenges, we collaborate closely with structural biologists and employ a combination of innovative approaches, including novel assay development, AI-powered protein-ligand interaction simulations, and high-throughput screening.
- Publications
Li, S.; Wang, N.; Yu, B.; Sun, W.; Wang, L. Genetically Encoded Chemical Cross-linking of Carbohydrate. Nature Chemistry, 2023,15,33–42. DOI: https://doi.org/10.1038/s41557-022-01059-z
Sun, W.; Wang, N.; Liu, H.; Yu, B.; Jin, L.; Ren, X.; Shen, Y.; Wang, L. Genetically Encoded Chemical Cross-linking of RNA in vivo. Nature Chemistry, 2022, 15,21–32. DOI: https://doi.org/10.1038/s41557-022-01038-4
Yu, B.; Li, S.; Tabata, T.; Wang, N.; Li, C.; Kumar, R.; Sun, W.; Liu, J.; Ott, M.; Wang, L. Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-CoV-2 and Variants. Chem, 2022, 8, 2766-2783. DOI: https://doi.org/10.1016/j.chempr.2022.07.012
Yu, B.; Kang, T.; Xu, Y.; Liu, Y.; Ma, Y.; Ke, B. Prodrugs of Persulfide and Sulfide: Is There a Pharmacological Difference between the Two in the Context of Rapid Exchanges among Various Sulfur Species in vivo? Angewandte Chemie International Edition. 2022, 61, e202201668. (Front cover)
Yu, B.; Choudhury, M.;1 Yang, X.;1 Benoit, S.; Womack, E.; Lyles, K; et al. Restoring and Enhancing the Potency of Existing Antibiotics against Drug-Resistant Gram-Negative Bacteria through the Development of Potent Small-Molecule Adjuvants. ACS Infectious Diseases. 2022, 8, 1491–1508.
Yu, B.; Yuan, Z.; Wang, B. Persulfide Prodrugs. in Pluth, M. & Wang, B. (Eds.), Hydrogen Sulfide: Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies. John Wiley & Sons, Hoboken, NJ, 2022. (Book chapter)
Liu, J.; Cao, L.; Klauser, P.; Cheng, R.; Berdan, V.; Sun, W.; Wang, N.; Ghelichkhani, F.; Yu, B.; Rozovsky, S.; Wang, L. A Genetically Encoded Fluorosulfonyloxybenzoyl-l-lysine for Expansive Covalent Bonding of Proteins via SuFEx Chemistry. Journal of the American Chemical Society. 2021, 143, 10341–10351.
Bakalarz, D.; Korbut, E.; Yuan, Z.; Yu, B.; Wójcik, D.; Danielak, A.; et al. Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier. International Journal of Molecular Sciences. 2021, 22, 5211.
Yu, B.; Yuan, Z.; Yang, X.; Wang, B. Prodrugs of Persulfides, Sulfur Dioxide, and Carbon Disulfide: Important Tools for Studying Sulfur Signaling at Various Oxidation States. Antioxidants & Redox signaling. 2020, 33, 1046-1059.
Li, S.; Yang, B.; Kobayashi, T.; Yu, B.; Wang, L. Genetically Encoding Thyronine for Fluorescent Detection of Peroxynitrite. Bioorganic & Medicinal Chemistry. 2020, 18, 115665.
Yang, X.; Pan, Z.; Choudhury, M.R.; Yuan, Z.; Anifowose, A.; Yu, B.; Wang, W.; Wang, B. Making Smart Drugs Smarter: The Importance of Linker Chemistry in Targeted Drug Delivery. Medicinal Research Reviews. 2020, 40, 2682-2713.
Liu, L.; Yu, B.; Han, M; Yuan, S; Wang, N. Mild Cognitive Impairment Understanding: An Empirical Study by Data-Driven Approach. BMC Bioinformatics. 2019, 20, 481.
Ji, X.; Aghoghovbia, R. E.; De La Cruz, L. K.; Pan, Z.; Yang, X.; Yu, B.; Wang, B. Click and Release: A High-Content Bioorthogonal Prodrug with Multiple Outputs. Organic Letters. 2019, 21, 3649-3652.
Ji, X.; Pan, Z.; Zheng, Y.; Yu, B.; De La Cruz, L. K.; Zheng, Y.; Ke, B.; Wang, B. Click and Release: Bioorthogonal Approaches to “On-demand” Activation of Prodrugs. Chemical Society Reviews. 2019, 48, 1077-1094.
Yu, B.; Zheng, Y.; Yuan, Z.; Li, S.; Zhu, H.; De La Cruz, L. K.; Zhang, J.; Ji, K.; Wang, S.; Wang, B. Toward Direct Protein S-Persulfidation: A Prodrug Approach That Directly Delivers Hydrogen Persulfide. Journal of the American Chemical Society. 2018, 140, 30–33.
Li, S.; Yu, B.; Wang, J.; Zheng, Y.; Zhang, H.; Walker, M. J.; et al. Biomarker-based Metabolic Glycan Labeling for Cancer Cell Imaging and Enhanced Immune Response. ACS Chemical Biology. 2018, 13, 1686–1694.
Yuan, Z.; Zheng, Y.; Yu, B.; S, Wang.; Yang, X.; Wang, B. Esterase-Sensitive Glutathione Persulfide. Organic Letters. 2018, 20, 6364-6367.
Zheng, Y.; Ji, X.; Yu, B.; Ji, K.; Gallo, D.; Csizmadia, E.; et al. Enrichment-Triggered Prodrug Activation Demonstrated Through Mitochondria-Targeted Delivery of Doxorubicin and Carbon Monoxide. Nature Chemistry. 2018, 10, 787–794.
Zheng, Y.; Yu, B.; De La Cruz, L. K.; Choudhury, M.R.; Chittavong, V.; Anifowose, A.; Wang, B. Toward Hydrogen Sulfide Based Therapeutics: Critical Drug Delivery and Developability Issues. Medicinal Research Reviews. 2018, 38, 57-100.
De La Cruz, L. K.; Benoit, S. L.; Pan, Z.; Yu, B.; Maier, R. J.; Ji, X.; Wang, B. Click, Release, and Fluoresce: A Chemical Strategy for a Cascade Prodrug System for Codelivery of Carbon Monoxide, a Drug Payload, and a Fluorescent Reporter. Organic Letters. 2018, 20, 897-900.
Zheng, Y.; Yu, B.; Li, Z.; Yuan, Z.; Organ, C. L.; Trivedi, R. K.; Wang, S.; Lefer, D. J.; Wang, B. An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species. Angewandte Chemie International Edition. 2017, 56, 11749 –11753.
Ji, X.; Ji, K.; Chittavong, V.; Yu, B.; Pan, Z.; Wang, B. An Esterase-Activated Click and Release Approach to Metal-Free CO-Prodrugs. Chemical Communications. 2017, 53, 8296-8299.
Li, Z.; Organ, C. L.; Trivedi, R. K.; Zheng, Y.; Yu, B.; Wang, B. Lefer, D. J. A Novel Hydrogen Sulfide Prodrug, BW-HP-202, Attenuates Myocardial Ischemia/Reperfusion Injury. The FASEB Journal. 2017, 31, 544-544.
Zheng, Y.; Yu, B.; Ji, K.; Pan, Z.; Chittavong, V.; Wang, B. Esterase-Sensitive Prodrugs with Tunable Release Rates and Direct Generation of Hydrogen Sulfide. Angewandte Chemie International Edition. 2016, 55, 4514-4518.
Ji, X.; Damera, K.; Zheng, Y.; Yu, B.; Otterbein, L. E.; Wang, B. Toward Carbon Monoxide-Based Therapeutics: Critical Drug Delivery and Developability Issues. Journal of Pharmaceutical Sciences. 2016, 105, 406-416.
Li, S.; Zhu, H.; Wang, J.; Wang, X.; Li, X.; Ma, C.; Wen, L.; Yu, B.; Wang, Y.; Li, J.; Wang, P. G. Comparative Analysis of Cu (I)-Catalyzed Alkyne-Azide Cycloaddition (CuAAC) and Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC) in O-GlcNAc Proteomics. Electrophoresis. 2016, 37, 1431–1436.
Damera, K.; Yu, B.; Wang, B. Stereoselective Synthesis of 1-Methyl-3´,4´,5´,6´- tetrahydrospiro[indoline-3,2´-pyran]-2-one Derivatives via Prins Cyclization. The Journal of Organic Chemistry. 2015, 80, 5457-5463.