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Biological Chemistry

Synthesizing Glycoproteins

Method combines solid-phase and bio-based peptide syntheses

by Jyllian N. Kemsley
February 9, 2009 | A version of this story appeared in Volume 87, Issue 6

Researchers at Bayreuth University, in Germany, have developed a new method for synthesizing homogeneous glycoproteins, combining solid-phase peptide synthesis with peptides produced in Escherichia coli to yield an N-glycosylated pancreatic ribonuclease C (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200804734 and 10.1002/anie.200804735). Led by chemistry professor Carlo Unverzagt, the researchers engineered E. coli to synthesize a precursor containing amino acid residues 40–124 of the protein. They then protected the peptide's seven cysteine groups, which are sensitive to oxidation, by converting them to mixed disulfides. Separately, the group used solid-phase synthesis to prepare two shorter peptides, one of protein residues 1–25 and one of residues 26–39, with a nonasaccharide attached to asparagine 34. They reconstituted the cysteines, ligated the fragments, and then folded the protein to yield 56% active enzyme. The approach of combining bio- and solid-phase synthesis—a method the researchers call "semisynthesis"—should allow easier preparation of larger glycoproteins compared with using chemical synthesis alone, Unverzagt says. In addition, disulfide modification of cysteine residues makes sensitive peptides more stable and easier to handle.


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