Mass spectrometric techniques and more particularly collision-induced dissociation (CID) experiments represent a powerful method for the determination of the primary sequence of (bio)molecules. However, the knowledge of the ion fragmentation patterns say the dissociation reaction mechanisms is a prerequisite to reconstitute the sequence based on fragment ions. Previous papers proposed that protonated peptoids dissociate following an oxazolone-ring mechanism starting from the O-protonation species and leading to high mass Y sequence ions. Here we revisit this backbone cleavage mechanism by performing CID and ion mobility experiments, together with computational chemistry, on tailor-made peptoids. We demonstrated that the B/Y cleavages of collisionally activated O-protonated peptoids must involve the amide nitrogen protonated structures as the dissociating species, mimicking the CID behavior of protonated peptides. Upon the nucleophilic attack of the oxygen atom of the N-terminal adjacent carbonyl group on the carbonyl carbon atom of the protonated amide, the peptoid ions directly dissociate to form an ion-neutral complex associating an oxazolone ion to the neutral truncated peptoid residue. Dissociation of the ion/neutral complex predominantly produces Y ions due to the high proton affinity of the secondary amide function characteristic of truncated peptoids. Whereas the production of Yx ions from acetylated peptoids also involves the B/Y pathway, the observation of abundant Yx ions from non-acetylated peptoid ions is shown in the present study to arise from an A1-Yx mechanism. The consecutive and competitive characters of the A1-Yx and the B/Y mechanisms are also investigated by drift time-aligned CID experiments.

中文翻译：

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碰撞诱导解离时质子化类肽的骨架裂解：竞争性和连续性 BY 和 A1-YX 反应。

质谱技术，尤其是碰撞诱导解离 (CID) 实验代表了确定（生物）分子一级序列的强大方法。然而，离子碎片模式的知识表明，解离反应机制是基于碎片离子重建序列的先决条件。以前的论文提出质子化的拟肽按照恶唑酮环机制从 O 质子化物质开始解离，并导致高质量的 Y 序列离子。在这里，我们通过在定制的拟肽上进行 CID 和离子迁移实验以及计算化学来重新审视这种骨架裂解机制。我们证明了碰撞激活的 O 质子化类肽的 B/Y 裂解必须涉及酰胺氮质子化结构作为解离物质，模拟质子化肽的 CID 行为。在质子化酰胺的羰基碳原子上的 N 端相邻羰基的氧原子亲核攻击后，拟肽离子直接解离形成离子中性复合物，将恶唑酮离子与中性截短的拟肽残基相关联。由于截短拟肽的二级酰胺功能特征的高质子亲和力，离子/中性复合物的解离主要产生 Y 离子。而从乙酰化类肽产生 Yx 离子也涉及 B/Y 途径，在本研究中，观察到来自非乙酰化类肽离子的大量 Yx 离子是由 A1-Yx 机制引起的。还通过漂移时间对齐的 CID 实验研究了 A1-Yx 和 B/Y 机制的连续性和竞争性。