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Ethylene glycol improves electrospray ionization efficiency in bottom-up proteomics

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Abstract

Liquid chromatography coupled online to nano-electrospray ionization (nESI) tandem mass spectrometry is the analytical workhorse in the field of proteome research. Dimethyl sulfoxide (DMSO) was recently shown to improve nESI efficiency by a factor of three to ten thus improving the sensitivity and coverage of proteomic experiments. However, relatively few investigations into which solvent additives promote nESI response have been performed at a proteomic scale. Here, we systematically evaluated the concept by screening about 30 compounds with various physico-chemical properties. Detailed further analysis showed that ethylene glycol performed similarly to DMSO and the results indicate that enhancing the nESI response of peptides by simple solvent additives is a valid and promising approach. Ethylene glycol may serve as a viable alternative to DMSO in applications where DMSO has disadvantages. In keeping with nESI theory, the key properties of an effective solvent additive for proteomic applications are a boiling point higher than water, low surface tension, and preferably high polarity for reversed phase LC-MS/MS applications.

Ethylene glycol substantially improves peptide ionization

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Acknowledgments

We gratefully acknowledge the funding from TUM University Foundation, Alexander von Humboldt Foundation, and Carl Friedrich von Siemens Foundation (to P.Y.). This work was also in part funded by the German Federal Ministry for Education and Research (grant 031L0008A). The authors also wish to thank Andreas Klaus for technical assistance, Chen Meng for help with data processing, and many of the current and former members of the laboratory for help with experiments and general discussion.

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Correspondence to Bernhard Kuster.

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Yu, P., Hahne, H., Wilhelm, M. et al. Ethylene glycol improves electrospray ionization efficiency in bottom-up proteomics. Anal Bioanal Chem 409, 1049–1057 (2017). https://doi.org/10.1007/s00216-016-0023-x

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