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首页> 外文期刊>Journal of mass spectrometry: JMS >Specific tandem mass spectrometric detection of AGE-modified arginine residues in peptides
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Specific tandem mass spectrometric detection of AGE-modified arginine residues in peptides

机译：肽中AGE修饰的精氨酸残基的特异性串联质谱检测

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摘要

Glycation is a non-enzymatic reaction of protein amino and guanidino groups with reducing sugars or dicarbonyl products of their oxidative degradation. Modification of arginine residues by dicarbonyls such as glyoxal and methylglyoxal results in formation of advanced glycation end-products (AGEs). In mammals, these modifications impact in diabetes mellitus, uremia, atherosclerosis and ageing. However, due to the low abundance of individual AGE-peptides in enzymatic digests, these species cannot be efficiently detected by LC-ESI-MS-based data-dependent acquisition (DDA) experiments. Here we report an analytical workflow that overcomes this limitation. We describe fragmentation patterns of synthetic AGE-peptides and assignment of modification-specific signals required for unambiguous structure retrieval. Most intense signals were those corresponding to unique fragment ions with m/z 152.1 and 166.1, observed in the tandem mass spectra of peptides, containing glyoxal- and methylglyoxal-derived hydroimidazolone AGEs, respectively. To detect such peptides, specific and sensitive precursor ion scanning methods were established for these signals. Further, these precursor ion scans were incorporated in conventional bottom-up proteomic approach based on data-dependent acquisition (DDA) LC-MS/MS experiments. The method was successfully applied for the analysis of human serum albumin (HSA) and human plasma protein tryptic digest with subsequent structure confirmation by targeted LC-MS/MS (DDA). Altogether 44 hydroimidazolone- and dihydroxyimidazolidine-derived peptides representing 42 AGE-modified proteins were identified in plasma digests obtained from type 2 diabetes mellitus (T2DM) patients. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译：糖基化是蛋白质氨基和胍基与它们的氧化降解的还原糖或二羰基产物的非酶促反应。二羰基化合物如乙二醛和甲基乙二醛对精氨酸残基的修饰导致形成高级糖基化终产物（AGEs）。在哺乳动物中，这些修饰影响糖尿病，尿毒症，动脉粥样硬化和衰老。但是，由于酶消化中单个AGE肽的丰度较低，因此无法通过基于LC-ESI-MS的数据依赖采集（DDA）实验有效地检测到这些物种。在这里，我们报告了克服了这一限制的分析工作流程。我们描述了合成AGE肽的片段化模式和明确结构检索所需的修饰特异性信号的分配。最强的信号是对应于m / z 152.1和166.1的独特片段离子的信号，在分别包含乙二醛和甲基乙二醛的氢咪唑酮AGEs的肽的串联质谱图中观察到。为了检测此类肽，针对这些信号建立了特异性和灵敏的前体离子扫描方法。此外，这些前体离子扫描结合了传统的自下而上的蛋白质组学方法，基于数据依赖采集（DDA）LC-MS / MS实验。该方法已成功用于人血清白蛋白（HSA）和人血浆蛋白胰蛋白酶消化物的分析，并通过靶向LC-MS / MS（DDA）进行了后续结构确认。在从2型糖尿病（T2DM）患者获得的血浆消化物中，共鉴定出代表42种AGE修饰蛋白的44种氢咪唑啉酮和二羟基咪唑烷衍生肽。版权所有（c）2015 John Wiley＆Sons，Ltd.

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