TY - JOUR
T1 - A Method for In-Depth Structural Annotation of Human Serum Glycans That Yields Biological Variations
AU - Song, Ting
AU - Aldredge, Danielle
AU - Lebrilla, Carlito B
PY - 2015/8/4
Y1 - 2015/8/4
N2 - Glycosylation is an important post-translational modification of proteins present in the vast majority of human proteins. For this reason, they are potentially new sources of biomarkers and active targets of therapeutics and vaccines. However, the absence of a biosynthetic template as in the genome and the general complexity of the structures have limited the development of methods for comprehensive structural analysis. Even now, the exact structures of many abundant N-glycans in serum are not known. Structural elucidation of oligosaccharides remains difficult and time-consuming. Here, we introduce a means of rapidly identifying released N-glycan structures using their accurate masses and retention times based on a glycan library. This serum glycan library, significantly expanded from a previous one covering glycans released from a handful of serum glycoproteins, has more than 170 complete and partial structures and constructed instead from whole serum. The method employs primarily nanoflow liquid chromatography and accurate mass spectrometry. The method allows us to readily profile N-glycans in biological fluids with deep structural analysis. This approach is used to determine the relative abundances and variations in the N-glycans from several individuals providing detailed variations in the abundances of the important N-glycans in blood. (Figure Presented).
AB - Glycosylation is an important post-translational modification of proteins present in the vast majority of human proteins. For this reason, they are potentially new sources of biomarkers and active targets of therapeutics and vaccines. However, the absence of a biosynthetic template as in the genome and the general complexity of the structures have limited the development of methods for comprehensive structural analysis. Even now, the exact structures of many abundant N-glycans in serum are not known. Structural elucidation of oligosaccharides remains difficult and time-consuming. Here, we introduce a means of rapidly identifying released N-glycan structures using their accurate masses and retention times based on a glycan library. This serum glycan library, significantly expanded from a previous one covering glycans released from a handful of serum glycoproteins, has more than 170 complete and partial structures and constructed instead from whole serum. The method employs primarily nanoflow liquid chromatography and accurate mass spectrometry. The method allows us to readily profile N-glycans in biological fluids with deep structural analysis. This approach is used to determine the relative abundances and variations in the N-glycans from several individuals providing detailed variations in the abundances of the important N-glycans in blood. (Figure Presented).
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U2 - 10.1021/acs.analchem.5b01340
DO - 10.1021/acs.analchem.5b01340
M3 - Article
C2 - 26086522
AN - SCOPUS:84938633596
VL - 87
SP - 7754
EP - 7762
JO - Industrial And Engineering Chemistry Analytical Edition
JF - Industrial And Engineering Chemistry Analytical Edition
SN - 0003-2700
IS - 15
ER -