Exploring the Effects of Methylation on the CID of Protonated Lysine: A Combined Experimental and Computational Approach

• Published in: Journal of the American Society for Mass Spectrometry Vol. 32; no. 11; pp. 2675 - 2684
• Main Authors: Lucas, Kenneth, Chen, Amy, Schubmehl, Megan, Kolonko, Kristopher J, Barnes, George L
• Format: Journal Article
• Language: English
• Published: American Chemical Society 03.11.2021
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1021/jasms.1c00225

We report the results of experiments, simulations, and DFT calculations that focus on describing the reaction dynamics observed within the collision-induced dissociation of l-lysine-H+ and its side-chain methylated analogues, N ε-methyl-l-lysine-H+ (Me1-lysine-H+), N ε,N ε-dimethyl-l-lysine-H+ (Me2-lysine-H+), and N ε,N ε,N ε-trimethyl-l-lysine-H+ (Me3-lysine-H+). The major pathways observed in the experimental measurements were m/z 130 and 84, with the former dominant at low collision energies and the latter at intermediate to high collision energies. The m/z 130 peak corresponds to loss of N­(CH3) n H3–n , while m/z 84 has the additional loss of H2CO2 likely in the form of H2O + CO. Within the time frame of the direct dynamics simulations, m/z 130 and 101 were the most populous peaks, with the latter identified as an intermediate to m/z 84. The simulations allowed for the determination of several reaction pathways that result in these products. A graph theory analysis enabled the elucidation of the significant structures that compose each peak. Methylation results in the preferential loss of the side-chain amide group and a reduction of cyclic structures within the m/z 84 peak population in simulations.