Increasing the Separation Capacity of Intact Histone Proteoforms Chromatography Coupling Online Weak Cation Exchange-HILIC to Reversed Phase LC UVPD-HRMS

Gargano, Andrea F. G.; Shaw, Jared B.; Zhou, Mowei; Wilkins, Christopher S.; Fillmore, Thomas L.; Moore, Ronald J.; Somsen, Govert W.; Pasa Tolic, Ljiljana

doi:10.1021/acs.jproteome.8b00458

Increasing the Separation Capacity of Intact Histone Proteoforms Chromatography Coupling Online Weak Cation Exchange-HILIC to Reversed Phase LC UVPD-HRMS

Journal Article · Tue Sep 18 00:00:00 EDT 2018 · Journal of Proteome Research

DOI:https://doi.org/10.1021/acs.jproteome.8b00458· OSTI ID:1507723

^[1]; ^[2]; ^[2]; Wilkins, Christopher S. ^[2]; Fillmore, Thomas L. ^[2]; Moore, Ronald J. ^[2]; Somsen, Govert W. ^[1]; Pasa Tolic, Ljiljana ^[2]

Center for Analytical Sciences Amsterdam (The Netherlands); Vrije Universiteit Amsterdam (The Netherlands)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Top-down proteomics is an emerging analytical strategy to characterize combinatorial protein post-translational modifications (PTMs). However, sample complexity and small mass differences between chemically closely related proteoforms often limit the resolution attainable by separations employing a single liquid chromatographic (LC) principle. In particular, for ultra-modified proteins like histones, extensive and time-consuming fractionation is needed to achieve deep proteoform coverage. Herein, we present the first online nano-flow comprehensive two-dimensional liquid chromatography (nLC×LC) platform top-down mass spectrometry analysis of histone proteoforms. The described two-dimensional LC system combines weak cation exchange chromatography under hydrophilic interaction LC conditions (i.e. charge- and hydrophilicity-based separation) with reversed phase liquid chromatography (i.e. hydrophobicity-based separation). The two independent chemical selectivities were run at nanoflows (300 nL/min) and coupled online with high-resolution mass spectrometry employing ultraviolet photodissociation (UVPD-HRMS). The nLC×LC workflow increased the number of intact protein masses observable relative to one-dimensional approaches and allowed characterization of hundreds of proteforms starting from limited sample quantities (~1.5 µg).

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1507723

Report Number(s):: PNNL-SA--138847

Journal Information:: Journal of Proteome Research, Journal Name: Journal of Proteome Research Journal Issue: 11 Vol. 17; ISSN 1535-3893

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
histones
online comprehensive two-dimensional liquid chromatography
post-translational modifications
top-down mass spectrometry
ultraviolet photodissociation

Increasing the Separation Capacity of Intact Histone Proteoforms Chromatography Coupling Online Weak Cation Exchange-HILIC to Reversed Phase LC UVPD-HRMS

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