Wang Group
Research Projects
N-Glycosylation is one of the most ubiquitous posttranslational modifications of proteins in eukaryotes. The Wang Lab is working at the interface of chemistry, biology, and immunology with a focus on the structures and functions of N-glycans, N-glycopeptides and N-glycoproteins. The covalent attachment of glycans adds a new level of structural and functional diversity of proteins and expands the biological information of an otherwise concise human genome.
Postdoctoral fellows and students in Wang group explore concepts and tools from various fields including synthetic chemistry, molecular biology, structural biology and immunology to understand the functional roles of glycans and glycoproteins in biological systems (host-pathogen interactions, symbiosis, and other important biological recognition processes). The group is also interested in translating the knowledge gained from functional and mechanistic studies into the design and development of more efficient therapeutic agents and vaccines against cancer and infectious diseases.
Synthesis of oligosaccharides, glycopeptides, and glycoproteins
Exploring new chemical and chemoenzymatic methods for the synthesis of biologically interesting oligosaccharides and homogeneous glycoproteins for probing functions.
Related Publications
Symbiotic signals
EPO Glycoproteins
a) Yamaguchi, T., Amin, M.N., Toonstra, C., Wang, L.X., “Chemoenzymatic Synthesis and Receptor Binding of Mannose-6-Phosphate (M6P)-Containing Glycoprotein Ligands Reveal Unusual Structural Requirements for M6P Receptor Recognition”, J. Am. Chem. Soc., 138, 12472-85 (2016).
b) Giddens, J.P., Lomino, J.V., Amin, M.N., Wang, L.X., “Endo-F3 glycosynthase mutants enable chemoenzymatic synthesis of core fucosylated tri-antennary complex-type glycopeptides and glycoproteins”, J. Biol. Chem., 291, 11064-11071 (2016).
c) Amin, M. N., Huang, W., Mizanur, R. M., Wang, L. X., “Convergent synthesis of homogeneous Glc1Man9GlcNAc2-protein and derivatives as ligands of molecular chaperones in protein quality control”, J. Am. Chem. Soc., 133, 14404–14417 (2011).
d) Wang, L.X., Amin, M.N., “Chemical and chemoenzymatic synthesis of glycoproteins for deciphering functions”, Chemistry & Biology, 21, 51-66(2014).
Antibody Glycoengineering
Understanding the key role glycosylation plays in the function of antibody mediated immunology.
IgG antibody
ADCC enhanced!
Related Publications
a) Li, T., Tong, X., Yang, Q., Giddens, J.P., Wang, L.X., “Glycosynthase mutants of endoglycosidase S2 show potent transglycosylation activity and remarkably relaxed substrate specificity for antibody glycosylation remodeling”, J. Biol. Chem., 291, 16508-16518 (2016).
b) Trastoy, B., Lomino, J.V., Pierce, B.G., Carter, L.G., Gunther, S., Giddens, J.P., Snyder, G.A., Weiss, T.M., Weng, Z., Wang, L.X., Sundberg, E.J., “Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies”, Proc. Natl. Acad. Sci. USA, 111, 6714-6719 (2014).
c) Huang, W., Giddens, J., Fan, S.Q., Toonstra, C., Wang, L.X., “Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions”, J. Am. Chem. Soc., 134, 12308−12318 (2012).
d) Zou, G., Ochiai, H., Huang, W., Yang, Q., Li, C., Wang, L. X., “Chemoenzymatic synthesis and Fcg receptor binding of homogeneous glycoforms of antibody Fc domain. Presence of a bisecting sugar moiety enhances the affinity of Fc to FcgIIIa receptor”, J. Am. Chem. Soc., 133, 18975-18991 (2011).
HIV Vaccine
Design, synthesis, and immunological studies of HIV vaccine targeting unique viral glycan and glycopeptide antigens.
HIV-1 V1V2 glycopeptide
Related Publications
a) Freund NT, et al and Nussenzweig MC, “Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller”, Science Translational Medicine, 9, eaal2144 (2017).
b) Toonstra, C., Amin, M.N., Wang, L.X., “Site-Selective Chemoenzymatic Glycosylation of an HIV-1 Polypeptide Antigen with Two Distinct N-Glycans via an Orthogonal Protecting Group Strategy”, J. Org. Chem., 81, 6176-6185 (2016).
c) Amin, M.N., McLellan, J.S., Huang, W., Orwenyo, J., Burton, D.R., Koff, W.C., Kwong, P.D., Wang, L.X., “Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies”, Nature Chem. Biol., 9, 521-526 (2013).
d) Wang, L.X., “Synthetic carbohydrate antigens for HIV vaccine design”, Current Opinion in Chemical Biology, 17, 997–1005 (2013).
Chemical Biology of Protein Glycosylation
Manipulating the biosynthesis and production of glycoproteins in cellular systems through biosynthetic pathway engineering and specific inhibition design
Related Publications
a) Yang, Q., Wang, L.X., “Mammalian α-1,6-fucosyltransferase (FUT8) is the sole enzyme responsible for the N-acetylglucosaminyltransferase I-independent core fucosylation of high-mannose N-glycans”, J. Biol. Chem., 291, 9356-9370 (2016).
b) Schwarz, F., Huang, W., Li, C., Schulz, B. L., Lizak, C., Palumbo, A., Numao, S., Neri, D., Aebi, M., Wang, L. X. “A combined method for producing homogeneous glycoproteins with eukaryotic N-glycosylation”, Nature Chem. Biol., 6, 264-266 (2010).