Alkali Metal Cationization of Tumor-associated Antigen Peptides for Improved Dissociation and Measurement by Differential Ion Mobility-Mass Spectrometry.

Alkali Metal Cationization of Tumor-associated Antigen Peptides for Improved Dissociation and Measurement by Differential Ion Mobility-Mass Spectrometry.
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DOI:
10.1021/acs.jproteome.0c00157
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发表时间:
2020-08-07
影响因子:
4.4
通讯作者:
Glish, Gary L.
Glish, Gary L.
中科院分区:
生物学2区
文献类型:
--
作者:
Keating, James E.;Chung, Chris;Chai, Shengjie;Prins, Jans F.;Vincent, Benjamin G.;Hunsucker, Sally A.;Armistead, Paul M.;Glish, Gary L.

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Tandem mass spectrometry (MS/MS) is a highly sensitive and selective method for detection of tumor associated peptide antigens. These short, non-tryptic sequences may lack basic residues, resulting in formation of predominantly [peptide+H]+ ions in electrospray. These singly charged ions tend to undergo inefficient dissociation, leading to issues in sequence determination. Addition of alkali metal salts to the electrospray solvent can drive formation of [peptide+H+metal]2+ ions that have enhanced dissociation characteristics relative to [peptide+H]+ ions. Both previously identified tumor-associated antigens and predicted neoantigen sequences were investigated. The previously reported rearrangement mechanism in MS/MS of sodium cationized peptides is applied here to demonstrate complete C-terminal sequencing of tumor associated peptide antigens. Differential ion mobility spectrometry (DIMS) is shown to selectively enrich [peptide+H+metal]2+ species by filtering out singly charged interferences at relatively low field strengths, offsetting the decrease in signal intensity associated with the use of alkali metal cations.
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