N–Cα Bond Cleavage of Zinc-Polyhistidine Complexes in Electron Transfer Dissociation Mediated by Zwitterion Formation: Experimental Evidence and Theoretical Analysis of the Utah–Washington Model

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• 作者：Daiki Asakawa ; Asuka Yamashita ; Shikiho Kawai ; Takae Takeuchi ; Yoshinao Wada
• 刊名：Journal of Physical Chemistry B
• 出版年：2016
• 出版时间：February 11, 2016
• 年：2016
• 卷：120
• 期：5
• 页码：891-901
• 全文大小：600K
• ISSN：1520-5207

文摘

Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of gas-phase ions are widely used for peptide/protein sequencing by mass spectrometry. To understand the general mechanism of ECD/ETD of peptides, we focused on the ETD fragmentation of metal–peptide complexes in the absence of remote protons. Since Zn²⁺ strongly binds to neutral histidine residues in peptides, Zn²⁺–polyhistidine complexation does not generate any remote protons. However, in the absence of remote protons, electron transfer to the Zn²⁺–polyhistidine complex induced the N–C_α bond cleavage. The formation pathway for the ETD products was investigated by density functional theory calculations. The calculations showed that the charge-reduced zinc–peptide radical, [M + Zn]^?+, can exist in the low-energy zwitterionic amide π* states, which underwent homolytic N–C_α bond dissociation. The homolytic cleavage resulted in the donation of an electron from the N–C_α bond to the nitrogen atom, producing an iminoenol c′ anion. The counterpart z^? radical contained a radical site on the α-carbon atom. The iminoenol c′ anion then abstracted a proton to presumably form the more stable amide c′ fragment. The current experimental and computational joint study strongly suggested that the N–C_α bond cleavage occurred through the aminoketyl radical-anion formation for Zn²⁺–polyhistidine complexes in ETD.