ECD OF COUMARIN TAGGED PEPTIDES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 电子俘获解离的机制目前是一个有很大争议的问题。几年前，我们发表了一篇论文，表明双电荷环肽的ECD产生了大量的次级片段，从而提出了自由基级联机制。这一机制的前提之一是形成一个自由基(那里没有争论)，并且它在启动键断裂之前存活很长时间(微秒到毫秒)。如果这是真的，合成一个可以稳定自由基的基团应该会减少裂解。 为了验证这一假设，将香豆素基团连接到P物质多肽上，并产生了这些修饰多肽的ECD谱。香豆素标签的加入消除了骨架切割，但增强了侧链切割，这支持FRC机制。这篇论文发表在《美国质谱学学会杂志》上。 将赖氨酸修饰成吡啶基的第二种固定电荷衍生物也得到了类似的结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mechanism of electron capture dissociation is a matter of substantial debate at the moment. Several years ago, we published a paper which showed that ECD of doubly charged cyclic peptides generated a very large number of secondary fragments and thus proposed a "free-radical cascade" mechanism. One of the premises of this mechanism is that a radical is formed (no debate there) and that it survives for a long time (microseconds to milliseconds) before initiating bond cleavages. If this is true, synthetically attaching a group which could stabilize a radical should reduce cleavages. In order to test this hypothesis, coumarin groups were attached to substance P peptides, and the ECD spectra of these modified peptides were generated. The addition of the coumarin tags eliminated backbone cleavages, but enhanced sidechain cleavages, which supports the FRC mechanism. This paper was published in the Journal of the American Society for Mass Spectroetry. A second fixed-charge derivative that modifies lysine into a pyridinyl group has been investigated with similar results.