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Updated: Mar 12, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Influence of Alkylammonium Acetate Buffers on Protein-Ligand Noncovalent Interactions Using Native Mass Spectrometry
Xiaoyu Zhuang1,2,3, Agni F M Gavriilidou1, Renato Zenobi4
1Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093, Zurich, Switzerland.
Abstract:
We investigate the influence of three volatile alkylammonium acetate buffers on binding affinities for protein-ligand interactions determined by native electrospray ionization-mass spectrometry (ESI-MS). Four different types of proteins were chosen for this study. A charge-reduction effect was observed for all the cases studied, in comparison to the ions formed in ammonium acetate solution. When increasing the collision energy, the complexes of trypsin and the ligand were found to be more stable when sprayed from alkylammonium acetate buffers than from ammonium acetate. The determined dissociation constant (Kd) also exhibited a drop (up to 40%) when ammonium acetate was replaced by alkylammonium acetate buffers for the case of lysozyme and the ligand. The prospective uses of these ammonium acetate analogs in native ESI-MS are discussed in this paper as well. Graphical Abstract ᅟ.
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