Research | Hongzhicao

Our Research

Our research focuses on the development of efficient and transferable methods for the systematic synthesis of complex human glycan libraries. We are interested in applying various organic synthesis concepts and methods to biocatalysis for the enzymatic modular assembly of complex glycans. We are also interested to the functional glycomics, carbohydrate-based drugs and other applications using well defined synthetic glycans.

1. Enzymatic Modular Assembly (EMA) of Human Glycans

KEY FEATURES：

• Each module contains a glycosyltranferase and a group of sugar nucleotide generation enzymes

• Readily available bacterial glycan biosynthesis enzymes are used in EMA

• In situ generation of the expensive sugar nucleotide glycosylation donors

• Highly efficient, highly selective and environment-friendly

2. Harnessing Enzyme Substrate Specificity through Chemical Evolution

Glycosyltransferases from bacteria are easily to obtain and the substrate flexibility of bacterial glycosyltransferases makes them suitable for oligosacchride construction. However, the substrate flexibility of bacterial glycosyltransferases also impedes the site-specific glycosylation in many cases, e.g. site-specific sialylation. We have been focusing on developing novel strategy to realize the regio-selective glycan assembly through substrate engineering.

Substrate Engineering for Regioselective Sialylation

J Am Chem Soc, 2014, 136, 5205

J. Am. Chem. Soc. 2019, 141, 4547−4552

3. Harnessing Enzyme Substrate Specificity through Direct Evolution

We also work on the redesign of bacterial glycosyltransferases for regioselective glycosylation.

Bacterial Sialyltransferase for Regioselective α2,6-sialylation

ACS Catal. 2018, 8, 7222-7227.

4. Functional Glycomics, Carbohydrate-Based Drugs and and Chemical Glycobiology

Base on the diverse glycan libraries we have constructed, multiple functional studies are now carried out in our lab. We hope to find out carbohydrate-related drug targets, develop carbohydrate-based drugs, and illuminate the bioactivity of glycans in life and disease.

Research Grants (PI, active or past)

1. National Natural Science Foundation of China (NSFC, 21877073), “Substrat-engineering directed regioselective alfa- 2,6-sialylation”, 1/2019 to 12/2022.

2. National Natural Science Foundation of China (NSFC, 21672128), “Diversity-oriented chemoenzymatic synthesis alfa-dystroglycan O-mannose glycans”, 1/2017 to 12/2020.

3. National Natural Science Foundation of China (NSFC, 21372145), “Chemoenzymatic synthesis and application of fluorinated tumor-associated carbohydrate antigens”, 1/2014 to 12/2017.

4. National Natural Science Foundation of China (NSFC, 21172135), “Glycoengineering of cisplatium-based drugs for targeted cancer treatment”, 1/2012 to 12/2015.

5. National Natural Science Foundation of China (NSFC, 20902087), “Chemoenzymatic synthesis of novel sialic acid- based probes”, 1/2010 to 12/2012.