Zhang Bo, Wang Yunjun, Zhou Bo-Wen, Cheng Jie, Xu Qi, Zhang Li, Sun Tuan-Qi, Zhang Jing, Guo Yin-Long
State Key Laboratory of Organometallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Department of Head and Neck Surgery, Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 270 Dongan Road, Shanghai 200032, China.
Anal Chem. 2022 Apr 26;94(16):6216-6224. doi: 10.1021/acs.analchem.1c05607. Epub 2022 Apr 14.
Specific locations of carbon-carbon double bonds (C═C) in lipids often play an essential role in biological processes, and there has been a booming development in C═C composition analysis by mass spectrometry. However, a universal derivatization and fragmentation pattern for the annotation of C═C positions in lipids is still challenging and attractive. To expand this field in lipidomics, a flexible and convenient -tosylaziridination method was developed, with high derivatization efficiency, sensitivity, and specificity. The derivatization was very fast (15 s), and C═C numbers as well as locations could be pinpointed specifically in tandem mass spectra. By qualitative and quantitative studies of paratumor and tumor thyroid tissues of human beings, the total content of unsaturated fatty acids was suggested to be increased in tumor tissues, and good correlations in and between lysophosphatidylcholines and phosphatidylcholines were revealed by Spearman analysis. Further studies of C═C isomers showed that -6/-3 ratios were closely associated with human thyroid tumorigenesis, and high ratios of -6/-3 isomers seemed to suffer a high risk of carcinogenesis. Other isomers were not very representative; however, C═C in -9/-7 could also be significant for oncology research. Generally, it is supposed that both total amounts and C═C isomer ratios were related to cancer, and -tosylaziridine derivatization could provide an alternative strategy for the C═C isomer study of disease models.
脂质中碳 - 碳双键（C═C）的特定位置在生物过程中往往起着至关重要的作用，并且通过质谱法进行C═C组成分析有了蓬勃发展。然而，用于脂质中C═C位置注释的通用衍生化和碎片化模式仍然具有挑战性且颇具吸引力。为了在脂质组学领域拓展这一方向，开发了一种灵活便捷的对甲苯磺酰氮丙啶化方法，该方法具有高衍生化效率、灵敏度和特异性。衍生化过程非常迅速（15秒），并且在串联质谱中可以明确确定C═C的数量以及位置。通过对人类甲状腺肿瘤旁组织和肿瘤组织的定性和定量研究，发现肿瘤组织中不饱和脂肪酸的总含量有所增加，并且通过斯皮尔曼分析揭示了溶血磷脂酰胆碱和磷脂酰胆碱内部以及它们之间存在良好的相关性。对C═C异构体的进一步研究表明，ω-6/ω-3比率与人类甲状腺肿瘤发生密切相关，高ω-6/ω-3异构体比率似乎具有较高的致癌风险。其他异构体不太具有代表性；然而，ω-9/ω-7中的C═C对于肿瘤学研究也可能具有重要意义。一般认为，总量和C═C异构体比率都与癌症有关，并且对甲苯磺酰氮丙啶衍生化可为疾病模型的C═C异构体研究提供一种替代策略。
