Scientists at Scripps Research describe new strategy for the synthesis of gly...( n glycoproteins are very much a part of...)

Some of the most intriguing problems in modern biology and medicine require scientists and doctors to synthesize proteins that have been modified with particular sugars attached in particular places. This presents a sticky problem because in the human body, the proteins are usually made first and then modified, and this modification is handled by a number of intricate mechanisms, not all of which may be reproduced in the test tube. Producing glycoproteins in the laboratory has been especially problematic.

Even when it is possible to directly synthesize particular glycosylated proteins in the test tube, producing them may be expensive, difficult, time-consuming, and not at all practical. Some glycosylated proteins are produced in microorganisms or cultures of eukaryotic cells, like yeast or Chinese hamster cells-an expensive and sometimes inexact process, which often involves difficult and expensive purification schemes.

Zhang, Schultz, Wong, and their colleagues have found another way-making homogeneous pools of glycosylated proteins in E. coli.

Bacterial cultures like E. coli have been used to produce proteins cheaply and easily for years, but it has never been possible to produce glycosylated proteins in them because bacteria don't normally have the same ability to attach sugars to proteins as eukaryotic cells do. The Scripps researchers solved this problem by modifying a form of E. coli to make homogeneous pools of glycosylated myoglobin protein with sugars attached at one desired position (see below: The Basis of the Technology).

Once the protein with the glycosyated amino acid was made and is
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Contact: Jason Bardi
jasonb@scripps.eduq
858-784-9254
Scripps Research Institute
15-Jan-2004