Simultaneous Determination of Absolute Configuration and Quantity of Lipopeptides Using Chiral Liquid Chromatography/Mass Spectrometry and Diastereomeric Internal Standards.
Simultaneous Determination of Absolute Configuration and Quantity of Lipopeptides Using Chiral Liquid Chromatography/Mass Spectrometry and Diastereomeric Internal Standards.
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DOI：
10.1021/acs.analchem.6b04901
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发表时间：
2017-02
影响因子：
7.4
通讯作者：
R. Nemati;Christopher Dietz;E. Anstadt;R. Clark;Michael Smith;F. Nichols;Xudong Yao
中科院分区：
文献类型：
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作者：
R. Nemati;Christopher Dietz;E. Anstadt;R. Clark;Michael Smith;F. Nichols;Xudong Yao
脂肽促进先天免疫反应，与疾病病理有关。为了研究脂肽的新作用，具有多个手性中心的立体异构体的精确测量是必不可少的，但也具有挑战性。本研究使用(3R)-和(3S)-（15-甲基-3-（（13-甲基十四烷基）氧）十六烷基）甘酰基-l-丝氨酸，简称为l-丝氨酸-(R+S)-脂质654，开发了一种结合手性液相色谱法、同位素标记的内标非对映体混合物和多重反应监测质谱法的方法。新方法允许同时确定细菌衍生的脂肽的立体异构体的绝对构型和数量。9株菌株的总脂质提取物含量不同，但只有l-丝氨酸-脂质654的(R)-异构体含量不同。所开发的方法还允许首次定量分析非磷脂作为蜂毒磷脂酶A2的新底物的水解。
Lipopeptides promote innate immune response and are related to disease pathology. To investigate the newly emerging roles of lipopeptides, accurate measurements of stereoisomers with multiple chiral centers are essential yet challenging. This work uses (3R)- and (3S)-(15-methyl-3-((13-methyltetradecanoyl)oxy)hexadecanoyl)glycyl-l-serine, abbreviated as l-serine-(R+S)-Lipid 654, to develop a method that combines chiral liquid chromatography, a diastereomeric mixture of isotopically labeled internal standards, and multiple reaction monitoring mass spectrometry. The new method allows for simultaneously determining the absolute configuration and quantity of stereoisomers of bacteria-derived lipopeptides. Total lipid extracts of nine evaluated bacteria strains had different amounts, but only the (R)-isoform of l-serine-Lipid 654. The developed method also allowed for the first quantitative analysis of hydrolysis of a nonphospholipid as a novel substrate of honey bee venom phospholipase A2.