Journal
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
Volume 29, Issue 5, Pages 817-826Publisher
SPRINGER
DOI: 10.1007/s13361-017-1787-8
Keywords
Discovery and targeted monitoring; Trapped ion mobility spectrometry; Mass; Spectrometry; Biomarker detection; Quantitative proteomics
Funding
- National Cancer Institute (NCI) through Leidos Biomedical Inc. [14X2333]
- National Institute of General Medicine [R00GM106414]
- DOE [DE-AC05-76RL01830]
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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.
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