The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Online Hydrophobic Interaction Chromatography–Mass Spectrometry for Top-Down Proteomics
Open accessAbstract
Recent progress in top-down proteomics has led to a demand for mass spectrometry (MS)-compatible chromatography techniques to separate intact proteins using volatile mobile phases. Conventional hydrophobic interaction chromatography (HIC) provides high-resolution separation of proteins under nondenaturing conditions but requires high concentrations of nonvolatile salts. Herein, we introduce a series of more-hydrophobic HIC materials that can retain proteins using MS-compatible concentrations of ammonium acetate. The new HIC materials appear to function as a hybrid form of conventional HIC and reverse phase chromatography. The function of the salt seems to be preserving protein structure rather than promoting retention. Online HIC-MS is feasible for both qualitative and quantitative analysis. This is demonstrated with standard proteins and a complex cell lysate. The mass spectra of proteins from the online HIC-MS exhibit low charge-state distributions, consistent with those commonly observed in native MS. Furthermore, HIC-MS can chromatographically separate proteoforms differing by minor modifications. Hence, this new HIC-MS combination is promising for top-down proteomics.
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“Hydrophobic interaction chromatography (HIC)-MS shows great promise for characterizing intact protein directly coupled to top-down MS [80].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [80]
In the citing paper
“Recently, high-throughput native separation techniques including GELFrEE,36 HIC,39,40 SEC,112 capillary zone electrophoresis (CZE),112 and IEX38 have efficiently aided in the analysis of heterogeneous protein mixtures.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [39]
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Cites
Proteoform: a single term describing protein complexity
The Consortium for Top Down Proteomics, Smith, L. M., & Kelleher, N. L. (2013) · Nature Methods · doi:10.1038/nmeth.2369 · Cited by 1,528
Native mass spectrometry: a bridge between interactomics and structural biology
Heck, A. J. R. (2008) · Nature Methods · doi:10.1038/nmeth.1265 · Cited by 766
Mapping intact protein isoforms in discovery mode using top-down proteomics
Tran, J. C., Zamdborg, L., Ahlf, D. R., Lee, J. E., Catherman, A. D., Durbin, K. R., Tipton, J. D., Vellaichamy, A., Kellie, J. F., Li, M., et al. (2011) · Nature · doi:10.1038/nature10575 · Cited by 665
Decoding protein modifications using top-down mass spectrometry
Siuti, N., & Kelleher, N. L. (2007) · Nature Methods · doi:10.1038/nmeth1097 · Cited by 503
Mass Spectrometry: Bottom-Up or Top-Down?
Chait, B. T. (2006) · Science · doi:10.1126/science.1133987 · Cited by 464
Hydrophobic interaction chromatography of proteins
Queiroz, J. A., Tomaz, C. T., & Cabral, J. M. S. (2001) · Journal of Biotechnology · doi:10.1016/s0168-1656(01)00237-1 · Cited by 451
Karve, T. M., & Cheema, A. K. (2011) · Journal of Amino Acids · doi:10.4061/2011/207691 · Cited by 381
Zhang, Z., Wu, S., Stenoien, D. L., & Paša‐Tolić, L. (2014) · Annual Review of Analytical Chemistry · doi:10.1146/annurev-anchem-071213-020216 · Cited by 336
High Throughput Characterization of Combinatorial Histone Codes
Young, N. L., DiMaggio, P. A., Plazas-Mayorca, M. D., Baliban, R. C., Floudas, C. A., & Garcia, B. A. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900238-mcp200 · Cited by 316
Top‐down proteomics in health and disease: Challenges and opportunities
Gregorich, Z. R., & Ge, Y. (2014) · PROTEOMICS · doi:10.1002/pmic.201300432 · Cited by 217
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Advanced structural elucidation of new antibody formats by mass spectrometry
Graf, T., Leiß, M., Haberger, M., & Bulau, P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822318-5.00005-3
Online Hydrophobic Interaction Chromatography–Mass Spectrometry (HIC–MS) Analysis of Proteins
Alpert, A. J. (2021) · LCGC North America · doi:10.56530/lcgc.na.bi6281a9
Self-citationRecent Advances in Top-Down Proteomics for Proteoform Analysis
Yu, J., Kim, M.-J., & Park, H.-M. (2023) · KSBB Journal · doi:10.7841/ksbbj.2023.38.1.12
Therapeutic Proteins and Hyphenated Methods for Characterization
Reusch, D., & Haberger, M. (2025) · doi:10.1002/9781394236145.ch5
Integrated NanoLC and UPLC-MS Platforms for Single Cell and Complex Mixture AnalysisPreprint
Ji, J., Han, E., Kwon, K., Kim, W., Park, Y., Son, A., & Kim, H. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5495747
Wike, C. J., & Alshami, A. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6459824
Wike, C., Alshami, A. S., Fischer, M. S., Pullela, A., & Ge, Y. (2026) · Journal of Chromatography A · doi:10.1016/j.chroma.2026.467272
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Metadata
- Authors
- Chen, B., Peng, Y., Valeja, S. G., Xiu, L., Alpert, A. J., & Ge, Y.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Alpert, Andrew J.
- Ge, Ying
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-01-14
- Volume
- 88
- Issue
- 3
- Pages
- 1885-1891
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC4947469
- OpenAlex
- W2229695971
- Cited by
- 110
- References
- 49
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 14 · 2021: 7 · 2020: 13 · 2019: 13 · 2018: 10 · 2017: 16 · 2016: 9
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH Office of the Director (S10OD01847)
- National Heart, Lung, and Blood Institute (R01HL096971, R01HL109810)
- National Institute of General Medical Sciences (R01GM11705)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- hydrophobic interaction chromatography, top-down proteomics, protein retention, reverse-phase chromatography, proteoforms, protein modification, native mass spectrometry, protein structure preservation, cell lysate analysis
- MeSH terms
- Animals, Cattle, Chickens, Chromatography, Chymotrypsinogen, Horses, Aprotinin, Lactoglobulins, Muramidase, Ribonuclease, Pancreatic, Mass Spectrometry, Trypsinogen, Internet, Proteomics, Hydrophobic and Hydrophilic Interactions
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