Sequence-Scrambling Fragmentation Pathways of Protonated Peptides
Sequence-Scrambling Fragmentation Pathways of Protonated Peptides
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DOI：
10.1021/ja805074d
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发表时间：
2008-12-31
影响因子：
15
通讯作者：
Paizs, Bela
中科院分区：
文献类型：
--
作者：
Bleiholder, Christian;Osburn, Sandra;Paizs, Bela
通过碰撞诱导解离（CID）和详细的分子力学和密度泛函理论（DFT）计算，研究了YAGFL-NH2、AGLFY-NH2、GFLYA-NH2、FLYAG-NH2和LYAGF-NH2的n端b和a片段的气相结构和断裂途径。我们的实验和理论结合的方法可以探测在b和a离子的CID中发生的乱序和重排反应。结果表明，上述肽的b(5)片段的低能CID产生几乎相同的解离模式。此外，在相似的实验条件下，质子化cyc/o-(YAGFL)的CID产生的片段离子丰度几乎相同。这表明，主要线性的b(5)离子发生了快速环化，CID谱确实是由环异构体的断裂行为决定的。这可以在各种酰胺键上打开，并且它的断裂行为只能通过假设大量的断裂线性结构来理解。我们的计算结果表明，质子化环-(YAGFL)在能量上优于线性b(5)异构体，完全支持这种环化-重开机制。此外，与传统的断键反应相比，重新开启环化的过渡结构对能量的要求更低，从而允许环状和线性异构体之间的快速相互转化。这种化学反应原则上会导致CID上的序列信息完全丢失，正如FLYAG-NH2的b(5)离子所记录的那样。上述肽的a(5)离子的CID产生片段离子分布，可以通过假设亲本群体的b型混乱和a -> a*型重排途径来解释（Vachet， R. W.; Bishop， B. M.; Erickson， B. W.; Glish， G. L. J.）。化学。社会科学，1997,119,5481)。虽然a离子很容易进行环化，但所产生的大环主要是重新打开以再生原始的线性结构。计算数据表明，线性a异构体的a—> a*型重排途径涉及裂解后质子结合二聚体中间体，其中片段重新结合，原c端片段转移到n端。
The gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH2, AGLFY-NH2, GFLYA-NH2, FLYAG-NH2, and LYAGF-NH2 were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows probing of the scrambling and rearrangement reactions that take place in CID of b and a ions. It is shown that low-energy CID of the b(5) fragments of the above peptides produces nearly the same dissociation patterns. Furthermore, CID of protonated cyc/o-(YAGFL) generates the same fragments with nearly identical ion abundances when similar experimental conditions are applied. This suggests that rapid cyclization of the primarily linear b(5) ions takes place and that the CID spectrum is indeed determined by the fragmentation behavior of the cyclic isomer. This can open up at various amide bonds, and its fragmentation behavior can be understood only by assuming a multitude of fragmenting linear structures. Our computational results fully support this cyclization-reopening mechanism by showing that protonated cyclo-(YAGFL) is energetically favored over the linear b(5) isomers. Furthermore, the cyclization-reopening transition structures are energetically less demanding than those of conventional bond-breaking reactions, allowing fast interconversion among the cyclic and linear isomers. This chemistry can lead in principle to complete loss of sequence information upon CID, as documented for the b(5) ion of FLYAG-NH2. CID of the a(5) ions of the above peptides produces fragment ion distributions that can be explained by assuming b-type scrambling of their parent population and a --> a*-type rearrangement pathways (Vachet, R. W.; Bishop, B. M.; Erickson, B. W.; Glish, G. L. J. Am. Chem. Soc. 1997, 119, 5481). While a ions easily undergo cyclization, the resulting macrocycle predominantly reopens to regenerate the original linear structure. Computational data indicate that the a --> a*-type rearrangement pathways of the linear a isomers involve post-cleavage proton-bound dimer intermediates in which the fragments reassociate and the originally C-terminal fragment is transferred to the N-terminus.