Glycosaminoglycans (GAGs) are linear and acidic polysaccharides. They are ubiquitous molecules, which are involved in a wide range of biological processes. Despite being structurally simple at first glance, with a repeating backbone of alternating hexuronic acid and hexosamine dimers, GAGs display a highly complex structure, which predominantly results from their heterogeneous sulfation patterns. The commonly applied method for compositional analysis of all GAGs is "disaccharide analysis." In this process, GAGs are enzymatically depolymerized into disaccharides, derivatized with a fluorescent label, and then analysed through liquid chromatography. The limiting factor in the high throughput analysis of GAG disaccharides is the time-consuming liquid chromatography. To address this limitation, we here utilized trapped ion mobility-mass spectrometry (TIM-MS) for the separation of isomeric GAG disaccharides, which reduces the measurement time from hours to a few minutes. A full set of disaccharides comprises twelve structures, with eight possessing isomers. Most disaccharides cannot be differentiated by TIM-MS in underivatized form. Therefore, we developed chemical modifications to reduce sample complexity and enhance differentiability. Quantification is performed using stable isotope labelled standards, which are easily available due to the nature of the performed modifications.

中文翻译：

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基于离子淌度质谱法的糖胺聚糖二糖分析

糖胺聚糖 (GAG) 是线性酸性多糖。它们是普遍存在的分子，参与广泛的生物过程。尽管乍一看结构简单，具有交替的己糖醛酸和己糖胺二聚体的重复主链，但 GAG 显示出高度复杂的结构，这主要是由于其异质硫酸化模式所致。所有 GAG 成分分析的常用方法是“二糖分析”。在此过程中，GAG 被酶解聚成二糖，用荧光标记衍生化，然后通过液相色谱进行分析。 GAG 二糖高通量分析的限制因素是耗时的液相色谱。为了解决这一限制，我们利用俘获离子淌度质谱 (TIM-MS) 来分离异构 GAG 二糖，从而将测量时间从几小时缩短到几分钟。全套二糖包含十二种结构，其中八种具有异构体。大多数未衍生形式的二糖无法通过 TIM-MS 进行区分。因此，我们开发了化学修饰来降低样品复杂性并增强可区分性。使用稳定同位素标记的标准品进行定量，由于所进行的修改的性质，这些标准品很容易获得。