Zhitao Li

- Assistant Professor, Organic Chemistry

• B.S., Fudan University, Shanghai, China 1996
• M.S., Peking University, Beijing, China, 1999, with Professor Wenting Hua
• Ph.D., Duke Unviersity, Durham, North Carolina, 1999-2003, with Professor Michael Pirrung
• Postdoc Fellow, National Cancer Institute, Maryland, 2003-2006, with Dr. Jeff Gildersleeve

The research of our group focus on the chemistry and biology of carbohydrate compounds (better known as sugar or saccharides). Carbohydrate is one the three major biopolymers in nature, along with peptide and nucleotides. Compared to other biopolymers, carbohydrate compounds are much more difficult to get, either through chemical synthesis or isolation from natural sources. However, the role of carbohydrate compounds in natural is as important as their counterparts of peptides and nucleotides. Carbohydrates are very important in biological processes like cell adhesion, recognition and migration. Carbohydrates are also involved in many diseases, such as cancer, AIDS, influenza and etc. Carbohydrate-containing natural products are also present in many natural products and drug molecules. Due to all these important functions, carbohydrate related research is currently one of the hottest fields in the pharmaceutical and biotech industry and basic research.

One of our research fields is the synthesis and biological study of carbohydrate containing natural product. Many carbohydrate natural products showed very interesting biological activities, but are difficult to isolate from nature. We will develop novel total synthesis of these natural products and synthesize a library of their analogues using combinatorial synthetic method. The natural product library will then be studied for their biological activities, including anti-tumor and anti-diabetic activities. An SAR study will be conducted by modification the structure of the molecules and more potent molecules will be designed and synthesized. This new generation of molecules will be further studied and the most potent compounds will be subjected to in vivo study or even clinical study.

Another project of our group will involve the development of new methodology for the oligosaccharide synthesis. One of the major obstacles for carbohydrate research is the difficulty of the synthesis of carbohydrate compounds. Unlike other biopolymers like peptides and nucleotides, which can be made by automatic synthesizer or through gene expression, carbohydrate compounds can only be made by hand. The synthesis of carbohydrate compounds is difficult because of the special structural feature of sugar molecules, which contains multiple hydroxyl groups and different chirality at the anomeric carbon. A good glycosylation reaction requires both high regioselectivity and stereoselectivity. There are a lot of known glycosylation methods, but none of them are “universal” or even close to “universal”. Synthesis of any oligosaccharides, sometimes even a disaccharide, requires a large amount of work. We are going develop a method with better stereoselectivity and better compatibility with different sugars. This kind of method will push us one step closer to the ultimate goal of automatic oligosaccharides synthesizer.

1. Lin, Bo; Pirrung, Michael C; Deng, Liu; Li, Zhitao; Liu, Yufa; Webster, Nicholas J G Neuroprotection by small molecule activators of the nerve growth factor receptor. The Journal of pharmacology and experimental therapeutics, 2007, 322(1), 59-69.
2. Manimala, Joseph C.; Roach, Timothy A.; Li, Zhitao; and Gildersleeve, Jeffrey C. “High-Throughput Carbohydrate Microarray Profiling of 27 Antibodies Demonstrates Widespread Specificity Problems.” Glycobiology, 2007, 17(8), 17C-23C.
3. Pirrung,Michael C.; Li, Zhitao; Hensley, Erika; Liu, Yufa; Tanksale,Aparna; Lin, Bo; Pai, Ashok; Webster, Nicholas J. G. “Parallel Synthesis of Indolylquinones and Their Cell -based Insulin Mimicry.” J. Comb. Chem. 2007, 9(5), 844-854.
4. Li, Zhitao; Gildersleeve, Jeffrey C. “An armed-disarmed approach for blocking aglycon transfer of thioglycosides.” Tetrahedron Lett. 2007, 48(4), 559-562.
5. Li, Zhitao and Gildersleeve, Jeff. "Mechanistic studies and methods to prevent aglycon transfer of thioglycosides," J. Amer. Chem. Soc. 2006, 128, 11612-11619.
6. Manimala, Joseph C.; Roach, Timothy A.; Li, Zhitao; Gildersleeve, Jeffrey C. “High-Throughput Carbohydrate Microarray Analysis of 24 Lectins”. Angew Chem Int Ed Engl. 2006, 45, 3607-3610.
7. Pirrung, Michael C.; Li, Zhitao; and Liu, Hao. “Synthetic Libraries of Fungal Natural Products,” in "Combinatorial Synthesis of Natural Product Based Libraries,” Boldi., A. M., Ed., CRC Press, NY, 2006, 209-226.
8. Manimala, Joseph; Li, Zhitao; Jain, Amit; VedBrat, Sharanjeet; and Gildersleeve, Jeffrey C. “Carbohydrate Array Analysis of Anti-Tn Antibodies and Lectins Reveals Unexpected Specificities: Implications for Diagnostic and Vaccine Development,” ChemBioChem, 2005, 6, 2229-2241.
9. Pirrung, Michael C.; Liu, Yufa; Deng, Liu; Halstead, Diana K.; Li, Zhitao; May, John F.; Wedel, Michael; Austin, Darrell A.; Webster, Nicholas J. G. “Methyl Scanning: Total Synthesis of Demethylasterriquinone B1 and Derivatives for Identification of Sites of Interaction with and Isolation of Its Receptor(s),” J. Amer. Chem. Soc. 2005, 127, 4609-4624.
10. Sohn, Jungsan; Kiburz, Brendan; Li, Zhitao; Deng, Liu; Safi, Alexias; Pirrung, Michael C.; Rudolph, Johannes. “Inhibition of Cdc25 Phosphatases by Indolyldihydroxyquinones,” J. Med. Chem., 2003, 46(13), 2580-2588.
11. Pirrung, Michael C.; Deng, Liu; Li, Zhitao; Park, Kaapjoo. “Synthesis of 2,5-Dihydroxy-3-(indol-3-yl)benzoquinones by Acid-Catalyzed Condensation of Indoles with 2,5-Dichlorobenzoquinone,” J. Org. Chem., 2002, 67(24), 8374-8388 ().
12. Pirrung, Michael C.; Li, Zhitao; Park, Kaapjoo; Zhu, Jin. “Total Syntheses of Demethylasterriquinone B1, an Orally Active Insulin Mimetic, and Demethylasterriquinone A1,”, J. Org. Chem., 2002, 67(23), 7919-7926.
13. Pirrung, Michael C.; Park, Kaapjoo; Li, Zhitao. “Synthesis of 3-indolyl-2,5-dihydroxybenzoquinones,” Org. Lett., 2001, 3(3), 365-367.
14. Wang, Shu; Li, Zhitao; Hua, Wenting. “Synthesis and characterization of fully conjugated schiff base macrocycles containing 1,3,4-oxadiazole moiety,” Synth. Comm., 2002, 32(21), 3339-3345 ().
15. Yang, Jun; Li, Zhitao; Hua, Wen-ting. “Synthesis of new macrocyclic polyamine having side-arms and macrocyclic polyether containing diaryl-1,3,4-oxadiazole,” Youji Huaxue, 2001, 21(6), 467-472.
16. Wang, Shu; Hua, Wen Ting; Li, Zhitao. “Synthesis and electrical conductivities of fully conjugated Schiff base macrocycles containing 1,3,4-oxadiazole” Chin. Chem. Lett.,, 10(5), 367-370.