Studying the biological functions of proteins is now an important task in the post-genomic era. However, more than 80% of human proteins have sugars attached to and are called glycoproteins. The process of protein glycosylation is known to play a central role in mediating protein function in living organisms.
Glycoproteins are shown in green, and yellow spots indicate the glycoproteins located in the Golgi
It is known that altered glycosylation is often associated with inflammation and cancer metastasis. Therefore, the detailed correlation between glycosylation and biological or pathological status is of great interest and may provide information for disease diagnosis and treatment. However, unlike DNA or protein molecules, cellular glycans are not produced by a template-driven process and are very complex in structure and heterogeneous in composition. It is quite a challenge to study the molecular details of glycosyl forms of proteins, and thus new tools for glycan tagging are needed and will have great value in delineating the molecular details of protein glycosylation to find out the mysteries behind the function of glycoprotein.
Sugar probe
In the research report, new chemical tools are designed and developed to probe glycoproteins for this purpose. First, sugar analogs are used to feed cells for labeling glycoproteins. The sugar analogs that are taken by cells are metabolized and utilized as substrates for incorporating into glycoproteins by glycosyltransferases. With the chemical functionality on sugar analogs, which allow for cell labeling with a very low toxicity, the labeled glycoproteins can then be specifically tagged on fluorescent probes or the probes used for affinity purification.
Team members
As reported by Dr. Chi-Huey Wong, a well known Chemist who is also currently the President of Academia Sinica, postdoctoral research fellow Dr. Tsui-Ling Hsu at Genomics Research Center in Academia Sinica, and collaborators at the Scripps Research Institute, the glycan tagging system allows for monitoring cell surface and intracellular trafficking of glycoproteins. In particular, it is useful for isolating and identifying the glycoproteins that are expressed differentially under various physiological or pathological conditions. This new innovative method together with another newly developed set of “sugar chips”, also reported by the Wong group and published online 31 January 2007 in Nature Protocols, has great potential for industrial use as high-throughput diagnostic tools for the analysis of post-translational protein glycosylation in disease states. The sugar probe study will be published online in the Early Edition of Proc. Natl. Acad. Sci. USA on February 5, 2007.
