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Pacific Northwest National Laboratory

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

TitleTowards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS
Publication TypeJournal Article
Year of Publication2018
AuthorsGarabedian A., Benigni P., Ramirez C.E, Baker E.S, Liu T., Smith R.D, Fernandez-Lima F.
JournalJ. Am. Soc. Mass Spectrom.

In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150-250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10-200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins. Graphical Abstract á…Ÿ.

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