多肽衍生物中自由基介导的选择性C—C键断裂及异构体区分  

Free Radical-Mediated Selective C—C Bond Cleavage and Differentiation of Isomers in Peptide Derivatives

作　　者：贾贺园 姚波 陈世稆 路时芳 曹洁 JIA He-yuan;YAO Bo;CHEN Shi-lyu;LU Shi-fang;CAO Jie(Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials,Key Laboratory of Cluster Science,Ministry of Education of China,School of Chemistry,Beijing Institute of Technology,Beijing100081,China)

机构地区：[1]北京理工大学化学与化工学院,原子分子簇科学教育部重点实验室,光电转换材料北京市重点实验室,北京100081

出　　处：《质谱学报》2022年第1期44-55,I0002,共13页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金项目(21371025)。

摘　　要：选择性C—C键断裂反应是化学领域的前沿课题,尤其对于生物大分子,该研究具有重要意义。由于化合物中活性相似的C—C键普遍存在,选择性断裂其中1个C—C键是一大难点。本文以非天然氨基酸组成的多肽衍生物为研究对象,采用TEMPO自由基引发剂策略,将邻甲基苯甲酰(Bz)自由基引入多肽分子(M),在气相中成功制备出[Bz-M+H]^(·+)自由基离子。通过串联质谱实验发现,该离子相对于质子化多肽分子[M+H]^(+)显示出更高的反应活性,具有更丰富的气相解离反应路径,其特征碎片离子[Bz·-a_(1)]^(+)和[(Bz-M+H)-HCOOEt]^(·+)可作为异构体区分和选择性C—C键断裂的灵敏探针,为质谱法区分多肽异构体和选择性C—C键断裂提供了思路和方法。The selective C—C bond activation is a frontier research topic and of great significance in the field of chemistry,especially for biosciences.Due to the existence of many C—C bonds with similar activities in compounds,it is difficult to selectively acti-vate one of the C—C bonds.In this paper,the newly synthesized peptide derivatives composed of unnatural amino acids were used as a subject to demonstrate how radical-mediated selective C—C bond activation and isomer differentiation work.TEMPO radi-cal initiator was employed to introduce o-methylbenzoyl(Bz)radical into the peptide derivatives,and successfully prepared[Bz-M+H]^(·+)radical ions in the gas phase.Through tandem mass spectrometry experiments,it had been found that[Bz-M+H]^(·+)showed higher reactivity than the protonated peptide molecule[M+H]^(+),giving a more diversified gas-phase dissociation reactions.The main fragmentation of[M+H]^(+)was the cleavage of amide bond to give rise to[y_(1)+2H]^(+)(m/z160.1340,RA 100%),a1+(m/z86.0972,RA 74%),and[(M+H)-HCOOEt]^(+)(m/z 199.1815,RA 52%).In contrast,the fragment ions of[Bz-M+H]^(·+)included[Bz·-a_(1)]^(+)(m/z 202.97),[Bz·-b_(1)]^(+)(m/z231.03),[Bz·-c_(1)+H]^(+)(m/z 133.95)and[(Bz-M+H)-HCOOEt]^(+)(m/z316.18,RA 100%).N-terminal fragments of[Bz-M+H]^(·+)were observed with the radical part·CH_(2)C_(6)H_(4)CO still attached to the fragmentation.To distinguish these ions from the normal fragments,the prefix Bz·was introduced,such as,[Bz·-a_(1)]^(+).More interestingly,[(Bz-M+H)-HCOOEt]^(+)was the base peak of[Bz-M+H]^(·+),which was produced by breaking the Cα—C adjacent to the ester group of peptide deriva-tive.In contrast,the relative abundance of[(M+H)-HCOOEt]^(+)from[M+H]^(+)was only 50%.The formation mechanism of[(M+H)-HCOOEt]^(+)had been experi-mentally confirmed to be completed by the two-step reaction of losing EtOH and CO successively.For isomers B1and B2,their CID spectra of[Bz-M+H]^(·+)had high simi-larity,but the abundance of fragment ion[Bz·-a_(1)]^(+)was obviously different(m/z20

关 键 词：电喷雾串联质谱(ESI-MS/MS) TEMPO-Bz-多肽衍生物 Bz-多肽自由基离子 异构体区分 选择性C—C键断裂 

分 类 号：O657.63[理学—分析化学]