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Selective Organic Precipitation/Extraction of Released N-Glycans Following Large-Scale Enzymatic Deglycosylation of Glycoproteins

✍ Scribed by Mary Frances Verostek; Catherine Lubowski; Robert B. Trimble


Book ID
102561916
Publisher
Elsevier Science
Year
2000
Tongue
English
Weight
317 KB
Volume
278
Category
Article
ISSN
0003-2697

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✦ Synopsis


A major difficulty with isolating enzymatically or chemically released oligosaccharides from large-scale glycoprotein deglycosylation reactions is the timeconsuming chromatography, desalting, and concentration steps required to prepare a glycan fraction of manageable proportions. To overcome these time and preparative chromatography equipment requirements, we have developed a rapid organic solvent precipitation/extraction procedure that allows sequential isolation of endo-␤-N-acetylglucosaminidase H (EC 3.2.1.96)-released high-mannose and hybrid, peptide-N 4 -(N-acetyl-␤-glucosaminyl) Asn amidase (EC 3.5.1.52)-released complex, and ␤-eliminated O-linked glycans without the need for intermediate chromatography, desalting, or concentration steps. The method involves precipitation of protein and released glycans at ؊20°C in 80% acetone and extraction of the glycans from the pellet with 60% aqueous methanol after each deglycosylation step. Three pools of essentially saltand detergent-free oligosaccharides (high-mannose/ hybrid, complex, and O-linked) can be isolated in a high yield in 4 days with this protocol, which has been extensively tested using bovine RNase B, human bile salt-stimulated lipase expressed in Pichia pastoris, hen ovalbumin, bovine fetuin, bovine thyroglobulin, and several invertase preparations from wild-type and mutant yeast strains.