One of the ways through which nature increases the functional diversity of the proteome is through a process known as posttranslational modifications, PTMs. Dimethylation of lysine, Kme2, and N-termini, NMe2, of proteins is a posttranslational modification which involves the catalytic attachment of two methyl groups onto lysine side chain or the N-termini amines.

Despite the surging interest towards this modification and its emergence as a key component of diverse set of biological events, its global identification has remained an unachieved goal. This is due to the lack of pan specific chemical tools for tagging of Kme2 and NMe2.

Our approach towards the global profiling of Kme2 and NMe2 involves the use of two independent tertiary amine trapping reactions: tertiary amine coupling via oxidation, TACO, and tertiary amine nucleophilic substitution, TANS.

Preliminary data highlights the efficiency of both techniques in tagging KMe2 and NMe2 in a pan-specific manner, with the added advantage of faster reaction kinetics and near-quantitative conversions. Our long-term goal is to utilize these technologies for the global profiling of KMe2 and NMe2 sites, and identification of disease related KMe2 and NMe2 biomarkers in the human proteome. To the best of our knowledge, this represents the first attempt towards labeling of KMe2 and NMe2 using a chemical strategy, thus the innovation of this work.