Bifunctional cleavable probes for in situ multiplexed glycan detection and imaging using mass spectrometry
Bifunctional cleavable probes for in situ multiplexed glycan detection and imaging using mass spectrometry
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使用质谱法进行原位多重聚糖检测和成像的双功能可裂解探针
DOI：
10.1039/c8sc04642e
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发表时间：
2019-02-28
期刊：
影响因子：
8.4
通讯作者：
Liu, Huwei
中科院分区：
文献类型：
--
作者：
Ma, Wen;Xu, Shuting;Liu, Huwei
糖链的原位分析具有重要意义，因为它们可以调节一系列的生物活性。糖基化异常与肿瘤的发生发展密切相关。在这项工作中，发展了双功能激光裂解质谱仪(LCMP)，用于激光解吸电离质谱仪(LDI-MS)原位检测细胞和组织中的葡聚糖。通过凝集素实现对糖链的特异性识别，并通过将检测糖链转化为质量标记来实现固有信号放大，克服了糖链电离效率低、质谱图复杂的缺点。由于合成LCMP和系列替代质量标签的路线简单且通用，因此多重聚糖图谱易于实现，从而提供了高灵敏度、低干扰和原位检测聚糖的方法。此外，作为一种优良的固有基质，LCMPs便于直接从细胞表面检测多糖和使用LDI-MS进行组织成像。为探讨糖基化与多种癌症之间的关系，本研究通过MS成像技术，严格显示了人癌及癌旁组织中固有的、精细的糖链分布。这种方法提供了一个基于LDI-MS的通用平台，用于快速和原位多重糖工程，从而为糖生物学和临床诊断提供了一个新的视角。
In situ analysis of glycans is of great significance since they mediate a range of biological activities. Aberrant changes of glycosylation are closely related to cancer onset and progression. In this work, bifunctional laser cleavable mass probes (LCMPs) were developed for in situ glycan detection from both cells and tissues using laser desorption ionization mass spectrometry (LDI-MS). Specific recognition of glycans was achieved by lectins, and inherent signal amplification was achieved by the conversion of the detection of glycans to that of mass tags which overcame the low ionization efficiency and complicated mass spectra of glycans. Multiplexed glycan profiling was easy to implement due to the simple and generic synthetic route to LCMPs and serial alternative mass tags, which offers high sensitivity, low interference and in situ detection of glycans. Moreover, as an excellent inherent matrix, LCMPs facilitated direct glycan detection from the cell surface and tissue imaging using LDI-MS. Intrinsic and fine glycan distribution in human cancer and paracancerous tissues was strictly demonstrated by MS imaging to explore the correlation between glycosylation and various cancers. This approach presented a versatile LDI-MS based platform for fast and in situ multiplexed glycan engineering, thus providing a new perspective in glycobiology and clinical diagnosis.