Synthesis of a deuterated disaccharide internal standard for LC-MS/MS quantitation of heparan sulfate in biological samples

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Carbohydrate Research Pub Date : 2024-09-07 DOI:10.1016/j.carres.2024.109270

Yuchen Pan, Qi Qi He, Norbert Wimmer, Vito Ferro

引用次数: 0

Abstract

High levels of heparan sulfate (HS) are a marker for several mucopolysaccharidosis (MPS) disorders which are lysosomal storage diseases caused by genetic defects in HS-degrading enzymes. Quantitation of HS in biological samples is therefore critical for diagnosis and evaluating the efficacy of new therapies. Herein we present the efficient synthesis of a butylated GlcN-GlcA disaccharide and its deuterated derivative for use as an internal standard in a quantitative mass spectrometry-based assay for analysis of HS following butanolysis. The synthesis features the stereoselective 1,2-cis glycosylation of a GlcA acceptor with a 6-O-benzoyl-2-deoxy-2-azido thioglucoside donor.

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合成用于 LC-MS/MS 定量生物样本中硫酸肝素的氚代二糖内标物

高水平的硫酸肝素（HS）是多种粘多糖病（MPS）的标志物，而粘多糖病是由HS降解酶的基因缺陷引起的溶酶体贮积疾病。因此，生物样本中 HS 的定量对于诊断和评估新疗法的疗效至关重要。在此，我们介绍了一种丁基化 GlcN-GlcA 二糖及其氚代衍生物的高效合成方法，该方法可用作基于质谱的定量测定中的内标，用于丁解后的 HS 分析。该合成方法的特点是将 GlcA 受体与 6-O-苯甲酰基-2-脱氧-2-叠氮硫代葡萄糖苷供体进行立体选择性 1,2-顺式糖基化。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".