Fragment Correlation Mass Spectrometry Enables Direct Characterization of Disulfide Bond Cleavage Pathways of Therapeutic Peptides,Analytical Chemistry

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Fragment Correlation Mass Spectrometry Enables Direct Characterization of Disulfide Bond Cleavage Pathways of Therapeutic Peptides
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-09-09 , DOI: 10.1021/acs.analchem.4c03202
Yangjie Li ₁ , Guy Cavet ₂ , Richard N. Zare ₁ , Taran Driver ₃

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Therapeutic peptides that are connected by disulfide bonds are often difficult to analyze by traditional tandem mass spectrometry without chemical modification. Using fragment correlation mass spectrometry, we analyzed 56 pairs of fragment ions generated from an equimolar (10 μM) mixture of three cyclic peptides, achieving sequence coverage of 86%, 100%, and 75% for octreotide, desmopressin, and the structural analogue of desmopressin, respectively. In all detected fragment ion pairs, only 20% of the fragment ions are terminal ions, with most of the measured ions only detected by fragment correlation mass spectrometry. From the peak volumes in the covariance map, we calculated branching ratios of each disulfide bond fragmentation pathway, providing a direct measurement of the probability of each fragmentation without requiring alteration of the chemical structure of the analytes.

中文翻译：

片段相关质谱能够直接表征治疗性肽的二硫键裂解途径

通过二硫键连接的治疗性肽通常难以通过未经化学修饰的传统串联质谱法进行分析。使用片段相关质谱法，我们分析了由三种环肽的等摩尔 (10 μM) 混合物产生的 56 对片段离子，奥曲肽、去氨加压素和结构类似物的序列覆盖率分别为 86%、100% 和 75%分别是去氨加压素。在所有检测到的碎片离子对中，只有20%的碎片离子是末端离子，大多数测量离子只能通过碎片相关质谱法检测到。根据协方差图中的峰值体积，我们计算了每个二硫键断裂途径的分支比，从而直接测量每个断裂的概率，而不需要改变分析物的化学结构。

更新日期：2024-09-09

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