Backbone cleavages of carbon monoxide and sequential loss and ammonia from protonated AGG: A combined tandem mass spectrometry, isotope labeling, and theoretical study

被引:39
作者
Bythell, Benjamin J.
Barofsky, Douglas F.
Pingitore, Francesco
Polce, Michael J.
Wang, Ping
Wesdemiotis, Chrys
Paizs, Bela
机构
[1] German Canc Res Ctr, Dept Mol Biophys, D-6900 Heidelberg, Germany
[2] Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA
[3] Univ Akron, Dept Chem, Akron, OH 44325 USA
关键词
D O I
10.1016/j.jasms.2007.03.029
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The fragmentation characteristics of protonated alanylglycylglycine, [AGG + H](+), were investigated by tandem mass spectrometry in MALDI-TOF/TOF, ion trap, and hybrid sector instruments. b(2) is the most abundant fragment ion in MALDI-TOF/TOF, ion trap, and hybrid sector metastable ion (MI) experiments, while y(2) is slightly more abundant than b(2) in collision activated dissociation (CAD) performed in the sector instrument. The A-G amide bond is cleaved on the a(1)-y(2) pathway resulting in a proton-bound dimer of GG and MeCH=NH. Depending on the fragmentation conditions employed, this dimer can then (1) be detected as [AGG + H - CO](+), (2) dissociate to produce y(2) ions, [GG + H](+), (3) dissociate to produce a(1) ions, [MeCH=NH + H](+), or (4) rearrange to expel NH3 forming a [AGG + H - CO - NH3](+) ion. The activation method and the experimental timescale employed largely dictate which of, and to what extent, these processes occur. These effects are qualitatively rationalized with the help of quantum chemical and RRKM calculations. Two mechanisms for formation of the [AGG + H - CO - NH3](+) ion were evaluated through nitrogen-15 labeling experiments and quantum chemical calculations. A mechanism involving intermolecular nucleophilic attack and association of the GG and imine fragments followed by ammonia loss was found to be more energetically favorable than expulsion of ammonia in an S(N)2-type reaction.
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页码:1291 / 1303
页数:13
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