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Selective Binding of a Lower Lysine Methylation State: An N,N-Dimethyllysine Selective Host Molecule and Its Use in Methyl Proteomics

preprint
submitted on 13.02.2020 and posted on 14.02.2020 by Alok Shaurya, Graham A. E. Garnett, Melissa J. Starke, Mark C. Grasdal, Charlotte C. Dewar, Aman K. Dheri, Euan L.S. Thomson, Fraser Hof

Post-translational modifications (PTMs) are critical controllers of protein functions. One set of important PTMs are N-methylated side chains of lysine and arginine, which exist in several functionally distinct forms. Multiple groups have demonstrated the selective binding of the most hydrophobic family member, trimethyllysine (Kme3), using various macrocyclic hosts, but the selective binding of lower methylation states remains challenging. Herein we report that a new calixarene modification – the installation of a sulfonate ester at the lower rim of p-sulfonatocalix[4]arene —efficiently generates a N,N-dimethyllysine (Kme2)-selective host. We characterize its binding behaviors in solution, and demonstrate its effectiveness in a pan-methyllysine enrichment step that enables the observation of hundreds of otherwise unobservable methylation marks in global proteomics experiments.

The submission includes a manuscript preprint, supporting information, and a tabulation of proteomics data.

Funding

NSERC Discovery Grant RGPIN2019-04086

Genome BC DIG9108

MITACS-Accelerate Industrial R&D Internship Program / Programme de Stage en R&D Industrielle MITACS-Accélération

Natural Sciences and Engineering Research Council

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History

Email Address of Submitting Author

fhof@uvic.ca

Institution

University of Victoria

Country

Canada

ORCID For Submitting Author

0000-0003-4658-9132

Declaration of Conflict of Interest

The authors declare no conflict of interest

Version Notes

Initial submission preprint

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