多级质谱法测定Axinastatin 1环肽序列及其断裂机理研究

对具有抗癌活性的海洋环肽Axinastatin 1进行化学合成. 采用多级质谱法对合成环肽进行序列测定. 线性前体测序依据b_x－y_z断裂路径, 在同一张MS²谱中利用b和y离子所提供序列信息的互补来实现. 环肽测序依据b_x→b_x－1断裂路径, 每一级MS由b离子的C端碰撞掉一个氨基酸残基直到MS⁶, 得到2套b离子, 根据它们所提供序列信息的互补可准确测定环肽序列并推断其环结构, 同时观察到b离子重排现象. 讨论了上述断裂与重排的路径和机理, 并利用半经验量子化学PM3和AM1两种算法计算了碎片的生成焓, 验证了路径的合理性. 由离子b_5PN的生成焓偏高和其重排间的联系尝试提出过渡结构假设.

Multistep Tandem Mass Spectrometry for Sequencing Cyclic Peptides Axinastatin 1 and Deducing Fragmentation Pathways

Marine cyclic peptide Axinastatin 1 was synthesized. In this process the peptide was sequenced by tandem mass spectrometry. Based on the b_x－y_z pathway, the linear peptide was sequenced through complementarities of the sequence information supplied by b and y ions in the same MS² spectrum. The cyclopeptide was sequenced based on the b_x→b_x－1 pathway. Two sets of b ions were obtained through sequentially removing one amino acid residue in each stage of MS/MS. According to above information, the cyclopeptide sequence was elucidated and the cyclic structure was concluded. The rearrangement of b ions was also observed. All the mechanisms were discussed and verified by semiempirical PM3 and AM1 quantum-chemical calculations. For the rearrangement of b ions, a hypothesis of translation structure was proposed.