title: Quantitative derivatization of sialic acids for the detection of sialoglycans by MALDI MS.
abstract: Recently, glycans have been recognized as valuable biomarkers for various disease states. In particular, sialoglycans, which have sialic acids at their terminal end, are likely to have relevance to diseases such as cancer and inflammation. Mass spectrometry (MS) has become an indispensable tool for biomarker discovery. However, matrix-assisted laser desorption ionization (MALDI) MS of sialoglycans normally causes loss of sialic acid. Methylesterification or amidation of carboxyl functionality in sialic acid has been reported to suppress the loss of sialic acids. We found that the modifications of alpha2,3-linked sialic acids proceed less efficiently than those at alpha2,6-linkages. Furthermore, the modifications of the alpha2,3-linked sialic acids are incomplete. This variability in the extent of derivatization presents a major problem in terms of glycan biomarker discovery using MALDI MS. In this study, we developed a novel amidation using acetohydrazide which can completely modify both types of linkages of sialoglycans. With the use of this method, we demonstrate MS profiling of N-linked glycans released from a bovine fetuin which is rich in alpha2,3-linked sialic acids.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toyoda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ito
authors.forename: Yu-ki
authors.initials: YK
authors.lastname: Matsuno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kameyama
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004952:Esters / Q000737:chemistry; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis* / Q000737:chemistry; D012794:Sialic Acids / Q000032:analysis* / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D000509:alpha-Fetoproteins / Q000032:analysis / Q000737:chemistry
chemical_list: D000577:Amides; D004952:Esters; D011134:Polysaccharides; D012794:Sialic Acids; D000509:alpha-Fetoproteins