Characteristic neutral loss of CH3CHO from Thr-containing sodium-associated peptides.
Characteristic neutral loss of CH3CHO from Thr-containing sodium-associated peptides.
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DOI：
10.1002/jms.3555
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发表时间：
2015-03
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通讯作者：
Huixin Wang;B. Wang;Zhonglin Wei;Yanwei Cao;X. Guan;Xinhua Guo
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作者：
Huixin Wang;B. Wang;Zhonglin Wei;Yanwei Cao;X. Guan;Xinhua Guo
在含苏氨酸的碱化多肽的MS/MS谱中观察到44Da的特征中性损失。在从头算理论的B3LYP/6-311G(d，p)水平上用串联质谱学和量子化学计算相结合的方法解释了这一碎裂途径。高分辨质谱仪数据表明，这种中性损失是从苏氨酸侧链上损失的乙醛，而不是二氧化碳。当苏氨酸残基远离C-末端以及当C-末端发生酯化时，这种中性损失的强度可以增强。乙醛损失的机理是采用McLafferty重排反应，该重排反应涉及一个质子从苏氨酸侧链的羟基转移到其C端邻近的羰基氧，导致Ca-Cβ键断裂。通过研究[GT(TBU)G+Na](+)多肽衍生物的裂解以及比较[GTGA+Na](+)的[M+Na-44](+)和[GGGA+Na](+)的[M+Na](+)的产物离子光谱，进一步支持了这一机理。在含有丝氨酸的多肽中也可以检测到类似的中性甲醛损失。我们的计算结果表明，最稳定的[GTG+Na](+)离子是以三齿电荷溶剂化结构存在的，导致44损失的解离是动力学和能量有利的。
A characteristic neutral loss of 44 Da is observed in the MS/MS spectra of Thr-containing sodiated peptides. A combination of tandem mass spectrometry and quantum chemical calculations calculated at the B3LYP/6-311G (d, p) level of ab initio theory is used to elucidate this fragmentation pathway. The high resolution mass spectrometry data indicate this neutral loss is acetaldehyde lost from the side chain of Thr rather than CO2. The intensity of this neutral loss can be enhanced when Thr residue is far from the C-terminus and when the C-terminus is esterified as well. The mechanism of the acetaldehyde loss is proposed to adopt a McLafferty-type rearrangement reaction, which involves a proton transfer from the hydroxyl of Thr side chain to its C-terminal neighboring carbonyl oxygen inducing the cleavage of the Ca-Cβ bond. This mechanism is further supported by examining the fragmentation of a [GT(tBu)G + Na](+) peptide derivative and by comparing the product ion spectra of [M + Na-44](+) of [GTGA + Na](+) with [M + Na](+) of [GGGA + Na](+). A similar neutral loss of HCHO can also be detected in Ser-containing peptides. Our computational results reveal that the most stable [GTG + Na](+) ion is present as a tridentate charge-solvated structure and the dissociation leading to the 44 loss is dynamically and energetically favorable.