Analytical Utility of Small Neutral Losses from Reduced Species in Electron Capture Dissociation Studied Using SwedECD Database

被引:40
作者
Falth, Maria [2 ]
Savitski, Mikhail M. [1 ]
Nielsen, Michael L. [1 ]
Kjeldsen, Frank [1 ]
Andren, Per E. [2 ]
Zubarev, Roman A. [1 ]
机构
[1] Uppsala Univ, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden
[2] Uppsala Univ, Dept Pharmaceut Biosci, SE-75123 Uppsala, Sweden
基金
瑞典研究理事会;
关键词
D O I
10.1021/ac800944u
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Small neutral losses from charge-reduced species [M + nH]((n-1)+center dot) is one of the most abundant fragmentation channels in both electron capture dissociation, ECD, and electron transfer dissociation, ETD. Several groups have previously studied these losses on particular examples. Now, the availability of a large (11491 entries) SwedECD database (http://www.bmms.uu.se/CAD/indexECD.html) of high-resolution ECD data sets on doubly charged tryptic peptides has made possible a systematic study involving statistical evaluation of neutral losses from [M + 2H](+center dot) ions. Several new types of losses are discovered, and 16 specific (>94%) losses are characterized according to their specificity and sensitivity, as well as occurrence for peptides of different lengths. On average, there is more than one specific loss per ECD mass spectrum, and two-thirds of all MS/MS data sets in SwedECD contain at least one specific loss. Therefore, specific neutral losses are analytically useful for improved database searching and de novo sequencing. In particular, N and GG isomeric sequences can be distinguished. The pattern of neutral losses was found to be remarkably dissimilar with the losses from radical z(center dot) fragment ions: e.g., there is no direct formation of w ions from the reduced species. This finding emphasizes the difference in fragmentation behaviors of hydrogen-abundant and hydrogen-deficient species.
引用
收藏
页码:8089 / 8094
页数:6
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