Targeted MultiNotch MS(3) Approach for Relative Quantification of N-Glycans Using Multiplexed Carbonyl-Reactive Isobaric Tags.
Targeted MultiNotch MS(3) Approach for Relative Quantification of N-Glycans Using Multiplexed Carbonyl-Reactive Isobaric Tags.
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DOI：
10.1021/acs.analchem.7b03289
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发表时间：
2018-01-16
影响因子：
7.4
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Chen B;Zhong X;Feng Y;Snovida S;Xu M;Rogers J;Li L
最近开发的和市售的羰基反应性串联质量标签（aminoxyTMT）能够通过比较报告离子强度对聚糖进行多重定量。然而，由于报告离子产率相对较低，特别是对于具有不稳定结构的聚糖，基于碰撞活化解离（CAD）MS/MS的氨氧基TMT定量仍然存在挑战。为了规避这一限制，我们利用N-聚糖分子的独特结构特征、共同的核心糖序列（HexNAc）2（Man）3和通过MS/MS从不同类型的前体产生的Yn离子的共同m/z，并设计了基于aminoxyTMT标记的Y1离子触发的靶向MultiNotch MS 3相对定量方法。该方法在nanoHILIC-Tribrid四极杆-离子阱-轨道阱平台上实施，该平台能够在高能碰撞解离（HCD）MS/MS扫描中通过Y1离子碎片离子质量预筛选aminoxyTMT标记的N-聚糖前体离子，并在MS/MS/MS扫描中共分离和共碎片化携带来自包含列表的同量异位标签的多个Yn碎片离子。通过使用从几种糖蛋白标准品和人血清蛋白中释放的N-聚糖进行系统优化和评估，我们证明了与传统的数据依赖性MS 2和Y1离子MS 3定量方法相比，Y1离子触发的靶向MultiNotch MS 3方法可提高相对定量的准确度、精密度和灵敏度。
The recently developed and commercially available carbonyl-reactive tandem mass tags (aminoxyTMT) enable multiplexed quantification of glycans through comparison of reporter ion intensities. However, challenges still exist for collision activated dissociation (CAD) MS/MS based quantification of aminoxyTMT due to the relatively low reporter ion yield especially for glycans with labile structures. To circumvent this limitation, we utilized the unique structural features of N-glycan molecules, the common core sugar sequence (HexNAc)2(Man)3, and common m/z of Yn ions generated from different types of precursors by MS/MS and designed a Y1 ion triggered, targeted MultiNotch MS3 relative quantification approach based on aminoxyTMT labeling. This approach was implemented on a nanoHILIC-Tribrid quadrupole-ion trap-Orbitrap platform, which enables prescreening of aminoxyTMT labeled N-glycan precursor ions by Y1 ion fragment ion mass in a higher-energy collisional dissociation (HCD) MS/MS scan and coisolation and cofragmentation of multiple Yn fragment ions that carry the isobaric tags from the inclusion list in the MS/MS/MS scan. Through systematical optimization and evaluation using N-glycans released from several glycoprotein standards and human serum proteins, we demonstrated that the Y1 ion triggered, targeted MultiNotch MS3 approach offers improved accuracy, precision, and sensitivity for relative quantification compared to traditional data-dependent MS2 and Y1 ion MS3 quantification methods.
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影响因子：
3.1
作者：
Tie, Cai;Zhang, Xin-Xiang
通讯作者：
Zhang, Xin-Xiang
影响因子：
7.4
作者：
Zhou S;Hu Y;Veillon L;Snovida SI;Rogers JC;Saba J;Mechref Y
通讯作者：
Mechref Y
影响因子：
7.4
作者：
Walker, S. Hunter;Budhathoki-Uprety, Januka;Novak, Bruce M.;Muddiman, David C.
通讯作者：
Muddiman, David C.
DOI：
10.1007/s13361-013-0681-2
发表时间：
2013-09
影响因子：
3.2
作者：
Walker, S. Hunter;Taylor, Amber D.;Muddiman, David C.
通讯作者：
Muddiman, David C.
影响因子：
7.4
作者：
Yang, Shuang;Yuan, Wei;Yang, Weiming;Zhou, Jianying;Harlan, Robert;Edwards, James;Li, Shuwei;Zhang, Hui
通讯作者：
Zhang, Hui