skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Journal of the American Society for Mass Spectrometry

Abstract. 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-TIMSCID- 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

Research Organization:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1437534
Report Number(s):
PNNL-SA-129610; 453040220
Journal Information:
Journal of the American Society for Mass Spectrometry, Vol. 29, Issue 5; ISSN 1044-0305
Publisher:
American Society for Mass Spectrometry
Country of Publication:
United States
Language:
English

References (54)

Ion dynamics in a trapped ion mobility spectrometer journal January 2014
High Resolution Trapped Ion Mobility Spectrometery of Peptides journal May 2014
VI. On the ratio of the velocities of the two ions produced in gases by Röntgen radiation; and on some related phenomena journal July 1898
Ion mobility–mass spectrometry: a new paradigm for proteomics journal February 2005
Kinetic Intermediates of Holo- and Apo-Myoglobin Studied Using HDX-TIMS-MS and Molecular Dynamic Simulations journal February 2015
Direct infusion mass spectrometry or liquid chromatography mass spectrometry for human metabonomics? A serum metabonomic study of kidney cancer journal January 2010
Ion Mobility-Mass Spectrometry (IM-MS) for Top-Down Proteomics: Increased Dynamic Range Affords Increased Sequence Coverage journal March 2012
Microheterogeneity within conformational states of ubiquitin revealed by high resolution trapped ion mobility spectrometry journal January 2015
Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts journal October 2015
Microtubules as a target for anticancer drugs journal April 2004
Toward Plasma Proteome Profiling with Ion Mobility-Mass Spectrometry journal November 2006
Mass-spectrometric exploration of proteome structure and function journal September 2016
Note: Integration of trapped ion mobility spectrometry with mass spectrometry journal December 2011
Resolving Isomeric Peptide Mixtures:  A Combined HPLC/Ion Mobility-TOFMS Analysis of a 4000-Component Combinatorial Library journal January 2002
Conformational Ordering of Biomolecules in the Gas Phase: Nitrogen Collision Cross Sections Measured on a Prototype High Resolution Drift Tube Ion Mobility-Mass Spectrometer journal February 2014
DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression journal February 2014
Improvement in Peptide Detection for Proteomics Analyses Using NanoLC−MS and High-Field Asymmetry Waveform Ion Mobility Mass Spectrometry journal April 2005
Structures of the kinetically trapped i-motif DNA intermediates journal January 2016
Ion Mobility-Mass Spectrometer Interface for Collisional Activation of Mobility Separated Ions journal January 2009
Gas-phase separations of protease digests journal November 1998
Improving the Efficiency of IMS−IMS by a Combing Technique journal March 2008
The Parafibromin Tumor Suppressor Protein Is Part of a Human Paf1 Complex journal January 2005
Overcoming Matrix Effects in Liquid Chromatography−Mass Spectrometry journal December 2008
Mechanistic investigation of ionization suppression in electrospray ionization journal November 2000
Microtubule-Associated Proteins as Targets in Cancer Chemotherapy journal May 2007
Collision-Induced Dissociation of Mobility-Separated Ions Using an Orifice-Skimmer Cone at the Back of a Drift Tube journal August 2001
Parallel Accumulation–Serial Fragmentation (PASEF): Multiplying Sequencing Speed and Sensitivity by Synchronized Scans in a Trapped Ion Mobility Device journal November 2015
Fundamentals of Trapped Ion Mobility Spectrometry journal October 2014
Biomolecule Analysis by Ion Mobility Spectrometry journal July 2008
Calmodulin Enhances the Stability of the Estrogen Receptor journal February 2001
The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics journal March 2014
Optimization of a matrix-assisted laser desorption ionization-ion mobility-surface-induced dissociation-orthogonal-time-of-flight mass spectrometer: simultaneous acquisition of multiple correlated MS 1 and MS 2 spectra journal November 2001
Flavin Adenine Dinucleotide Structural Motifs: From Solution to Gas Phase journal September 2014
Mapping the human plasma proteome by SCX-LC-IMS-MS journal July 2007
Gas-phase separation using a trapped ion mobility spectrometer journal June 2011
Targeted High-Resolution Ion Mobility Separation Coupled to Ultrahigh-Resolution Mass Spectrometry of Endocrine Disruptors in Complex Mixtures journal April 2015
Direct Observation of Differences of Carotenoid Polyene Chain cis / trans Isomers Resulting from Structural Topology journal January 2014
Simultaneous fragmentation of multiple ions using IMS drift time dependent collision energies journal March 2008
Fast screening of polycyclic aromatic hydrocarbons using trapped ion mobility spectrometry – mass spectrometry journal January 2014
Parallel accumulation for 100% duty cycle trapped ion mobility-mass spectrometry journal February 2017
Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry journal March 2016
Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography–electrospray–tandem mass spectrometry journal April 2005
Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space journal March 2015
Progesterone Receptor Membrane Component 1 (Pgrmc1): A Heme-1 Domain Protein That Promotes Tumorigenesis and Is Inhibited by a Small Molecule journal February 2010
Effects of Traveling Wave Ion Mobility Separation on Data Independent Acquisition in Proteomics Studies journal May 2013
Mass Spectrometry on the Chromatographic Time Scale: Realistic Expectations journal August 1983
Parafibromin expression in breast cancer: a novel marker for prognostication? journal September 2007
A Split-Field Drift Tube for Separation and Efficient Fragmentation of Biomolecular Ions journal November 2003
Assessing the Peak Capacity of IMS−IMS Separations of Tryptic Peptide Ions in He at 300 K journal January 2007
On the structural denaturation of biological analytes in trapped ion mobility spectrometry – mass spectrometry journal January 2016
Isomerization Kinetics of AT Hook Decapeptide Solution Structures journal January 2014
Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site journal July 2011
An investigation of the mobility separation of some peptide and protein ions using a new hybrid quadrupole/travelling wave IMS/oa-ToF instrument journal March 2007
Reversed-phase chromatography with multiple fraction concatenation strategy for proteome profiling of human MCF10A cells journal April 2011

Similar Records

Identification of mammalian cell lines using MALDI-TOF and LC-ESI-MS/MS mass spectrometry
Journal Article · Sat Apr 15 00:00:00 EDT 2006 · Journal of the American Society for Mass Spectrometry · OSTI ID:1437534

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry
Journal Article · Sun Sep 25 00:00:00 EDT 2016 · Molecular and Cellular Proteomics · OSTI ID:1437534

The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification
Journal Article · Fri Dec 04 00:00:00 EST 2015 · Expert Review of Proteomics · OSTI ID:1437534

Related Subjects