Scientists at Scripps Research describe new strategy for the synthesis of glycoproteins

A team of investigators at The Scripps Research Institute and its Skaggs Institute for Chemical Biology in La Jolla, California has developed a new way of making glycoproteins-proteins with carbohydrates (sugars) attached.

Methods for making glycosylated proteins are important to scientists who want to understand the role of carbohydrates in protein structure and function, since the human body contains many heavily glycosylated proteins, including antibodies, hormones, and immune system proteins like cytokines and interleukins. These methods are also of interest to doctors, since pharmaceuticals are often heavily glycosylated proteins (e.g., erythropoietin, which is useful for treating anemia, cancer, and AIDS).

"In the future, you will see more and more proteins [coming forth] as drug candidates, mainly because of advances in genomic research," says Chi-Huey Wong, Ph.D, who is Ernest W. Hahn Professor and Chair in Chemistry at Scripps Research, "and most of these proteins have sugars on them."

Led by Professor Wong, Professor Peter G. Schultz, Ph.D., who holds the Scripps Family Chair in Chemistry at Scripps Research, and Scripps Research Associate Zhiwen Zhang, Ph.D., the team of scientists discovered a new way of synthesizing glycoproteins, and they report their strategy in the latest issue of the journal Science.

The strategy, which avoids some of the bottlenecks of previous methods, involves using a modified form of the bacterium Escherichia coli to express a glycosylated form of the protein myoglobin. The E. coli was evolved so that it would insert a glycosylated amino acid into the sequence of the myoglobins as they were being produced.

The Tough Task of Making Glycoproteins
Glycoproteins are basically proteins that have been modified so that one or more carbohydrates (sugars) are attached to nitrogen or oxygen atoms within the protein's amino acids.

The modifications o

Contact: Jason Bardi
Scripps Research Institute

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