个人简介

B.S., Second Military Medical University, China, 1984 Ph.D., Institute of Organic Chemistry, Polish Academy of Sciences, 1991 Postdoctoral Fellow, Shanghai Institute of Organic Chemistry, 1991-1994

研究领域

Natural product synthesis/glycoconjugate vaccines/new synthetic methodologies for oligosaccharides and glycopeptides/carbohydrate-based biomimetic materials/and development of antitumor therapies

Our research program is engaged in a wide range of problems, from chemical synthesis of natural products to development of novel therapies for human diseases. These research efforts are centered on carbohydrates, since carbohydrates play a pivotal role in various biological and pathological processes. Projects under investigation include: 1. Carbohydrate-based cancer vaccines or cancer immunotherapies. This project targets at the aberrant carbohydrates expressed on tumor cells, namely tumor-associated carbohydrate antigens (TACAs). TACAs are synthesized and then linked to a carrier protein to form glycoconjugates that are studied as vaccines to stimulate the immune system of cancer patients for elimination of cancer. Moreover, cell glycoengineering technique is employed to biochemically modify TACAs on tumor cells, which marks tumors for more effective immune recognition and reaction. Vaccines derived from modified forms of TACAs are more immunogenic than native TACAs. The combination of glycoengineering with modified carbohydrate vaccine can expand the scope of carbohydrate-based cancer immunotherapy. 2. New methodologies for oligosaccharide and glycopeptide synthesis. This research is focused on the development of new, effective methods for solid-phase oligosaccharide synthesis and solution-phase glycopeptide synthesis. The latter usesuses unprotected the glycosyl amino acids as key the building blocks to enable solid-state isolation of synthetic intermediates. 3. Total synthesis of natural products. One of the targets is CD52 antigen, a glycosylphosphatidylinositol (GPI)-anchored glycopeptide expressed on human lymphocyte and sperm cells. CD52 plays a critical role in human immune and reproduction systems. After various glycoforms of CD52 are synthesized, NMR is used to examine their structures. The structure-activity relationship studies of CD52 aim at probing the functions of GPI. Another synthetic target is OSW-1, an especially potent antitumor agent. The biological studies of OSW-1 and its analogs will help discover new antitumor drugs.

近期论文

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Swarts, B. M.; Guo, Z. "Synthesis of Glycosylphosphatidylinositol (GPI) Anchors Bearing Unsaturated Lipid Chains", J. Am. Chem. Soc., 2010, 132, 6648. Wu, Z. ; Guo, X.; Wang, Q. ; Swarts, B. M.; Guo, Z. "Sortase A-Catalyzed Transpeptidation of Glycosylphosphatidylinositol Derivatives for Chemoenzymatic Synthesis of GPI-Anchored Peptides/Proteins", J. Am. Chem. Soc., 2010, 132, 1567. Tang, S.; Wang, Q., Guo, Z. "Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor-Associated Carbohydrate Antigen", Chem. Eur. J., 2010, 16, 1319. Wang, Q.; Guo, Z. "Synthesis of a Monophosphoryl Lipid A Derivative and Its Coupling to a Tumor-Associated Carbohydrate Antigen for Cancer Vaccine Development", Chem. Commun., 2009, 5536. Guo, X.; Wang, Q.; Swarts, B.M.; Guo, Z. "Sortase-Catalyzed Peptide-Glycosylphosphatidylinositol (GPI) Analog Ligation", J. Am. Chem. Soc, 2009, 131, 9878. Xue, J.; Liu, P.; Pan, Y.; Guo, Z. "A Total Synthesis of OSW-1", J. Org. Chem., 2008, 73, 157. Wang, Q.; Zhang, J.; Guo, Z. "Efficient Glycoengineering of GM3 on Melanoma Cell and Monoclonal Antibody-Mediated Selective Killing of the Glycoengineered Cancer Cell", Bioorg. Med. Chem., 2007, 15, 7561. Chefalo, P; Pan, Y.; Nagy, N.; Harding, C.; Guo, Z. "Effective Metabolic Engineering of GM3 on Tumor Cells by N-Phenylacetyl-D-mannosamine", Biochemistry, 2006, 45, 3733. Yan, F.; Xue, J.; Zhu, J.; Marchant, R.; Guo, Z. "Synthesis of a Lipid Conjugate of SO3Lea and Its Enhancement on Binding of Liposome to Activated Platelets", Bioconjugate Chem., 2005, 16, 90. Pan, Y.; Chefalo, P; Nagy, N.; Harding, C.; Guo, Z. "Synthesis and Immunological Properties of N-Modified GM3 as Therapeutic Cancer Vaccines", J. Med. Chem., 2005, 48, 875. Shao, N.; Xue, J.; Guo, Z. "Chemical Synthesis of a Skeleton Structure of Sperm CD52 - A GPI-Anchored Glycopeptide", Angew. Chem. Int. Ed., 2004, 43, 1569. Xue, J.; Guo, Z. "Convergent Synthesis of a GPI Containing an Acylated Inositol", J. Am. Chem. Soc., 2003, 125, 16334.