基于多肽化的MALDI-TOF-MS测定小分子化合物的分析方法
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摘要
基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)分析小分子化合物一直是分析科学领域一个不小的挑战。本文基于多肽质谱探针,建立了MALDI-TOF-MS分析小分子化合物的方法。通过多肽化,小分子目标分析物的分子量增大,从而避免了MALDI-MS分析中低分子量区域严重的基质干扰。多肽通常在MALDI-MS分析中具有很好的信号响应,因此多肽化的方法赋予了小分子分析物很好的检测灵敏度。为了验证这一方法的可行性,我们分析了小分子的醛类和巯基类化合物。我们的结果表明多肽化后的醛类和巯基类化合物能轻易地被MALDI-MS检测到,从而实现小分子化合物的灵敏、高效检测。另外,利用多肽化的方法,生物样品中的目标分析物也能被清楚地检测到。本文建立的多肽化方法是一种普适性的方法,能被拓展应用于一系列小分子化合物的MALDI-MS高灵敏分析,例如代谢组学等研究中有一定潜在应用价值。
Determination of low-molecule-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS) has been a great challenging in analytical research field.Here we developed a universal peptide-based derivatization(peptidylation) strategy for the sensitive analysis of low-molecule-weight compounds by MALDI-TOF-MS.Upon peptidylation,the molecule weights of target analytes increase,thus avoiding the serious matrix ion interference in low-molecule-weight region in MALDI-TOF-MS.Since peptides typically exhibit good signal response during MALDI-TOF-MS analysis,peptidylation endows the high detection sensitivities of low-molecule-weight analytes.As a proof-of-concept,we analyzed low-molecule-weight compounds of aldehydes and thiols by the developed peptidylation strategy.Our results showed that aldehydes and thiols can be readily determined upon peptidylation,thus realizing the sensitive and efficient determination of low-molecule-weight compounds by MALDI-TOF-MS.Moreover,target analytes also can be unambiguously detected in biological samples using the peptidylation strategy.The established peptidylation strategy is a universal strategy and can be extended to the sensitive analysis of various low-molecule-weight compounds by MALDI-TOF-MS,which may be potentially used in area such as metabolomics.
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