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

14 February 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


Host-guest chemistry
Supramolecular chemistry
Post-translational modifications
Affinity enrichment


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