Linkage-Specific in Situ Sialic Acid Derivatization for N-Glycan Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded Tissues

被引：133

作者：

Holst, Stephanie ^{[1
]}

Heijs, Bram ^{[1
]}

de Haan, Noortje ^{[1
]}

van Zeijl, Rene J. M. ^{[1
]}

Briaire-de Bruijn, Inge H. ^{[2
]}

van Pelt, Gabi W. ^{[3
]}

Mehta, Anand S. ^{[4
]}

Angel, Peggy M. ^{[5
]}

Mesker, Wilma E. ^{[3
]}

Tollenaar, Rob A. ^{[3
]}

Drake, Richard R. ^{[5
]}

Bovee, Judith V. M. G. ^{[2
]}

McDonnell, Liam A. ^{[1
,2
,6
]}

Wuhrer, Manfred ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Ctr Prote & Metabol, NL-2333 ZA Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZA Leiden, Netherlands

[3] Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands

[4] Drexel Univ, Coll Med, Dept Microbiol & Immunol, 245 N 15th St, Philadelphia, PA 19102 USA

[5] Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA

[6] Croce Rossa Italiana, Fdn Pisana Sci ONLUS, Via Panfilo Castaldi 2, I-56121 Pisa, Italy

来源：

ANALYTICAL CHEMISTRY | 2016年 / 88卷 / 11期

基金：

美国国家卫生研究院;

关键词：

SOLID-PHASE PERMETHYLATION; SIALYLATED GLYCANS; LINKED GLYCANS; GLYCOSYLATION; STABILIZATION; BREAST; OLIGOSACCHARIDES; MICRODISSECTION; MECHANISMS;

D O I：

10.1021/acs.analchem.6b00819

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a rapidly evolving field in which mass spectrometry techniques are applied directly on tissues to characterize the spatial distribution of various molecules such as lipids, protein/peptides, and recently also N-glycans. Glycans are involved in many biological processes and several glycan changes have been associated with different kinds of cancer, making them an interesting target group to study. An important analytical challenge for the study of glycans by MALDI mass spectrometry is the labile character of sialic acid groups which are prone to in-source/postsource decay, thereby biasing the recorded glycan profile. We therefore developed a linkage-specific sialic acid derivatization by dimethylamidation and subsequent amidation and transferred this onto formalin-fixed paraffin-embedded (FFPE) tissues for MALDI imaging of N-glycans. Our results show (i) the successful stabilization of sialic acids in a linkage specific manner, thereby not only increasing the detection range, but also adding biological meaning, (ii) that no noticeable lateral diffusion is induced during to sample preparation, (iii) the potential of mass spectrometry imaging to spatially characterize the N-glycan expression within heterogeneous tissues.

引用

页码：5904 / 5913

页数：10