Selective Molecular Box

The methylation states of Lys and Arg represent a particularly challenging set of targets to distinguish selectively in water using synthetic receptors. To date, trimethyllysine, Kme3, is the only post translational modification, PTM, of the eight possible methylation states of Lys and Arg that can be recognized selectively.

In a paper published in Angewandte Chemie, International Edition, graduate student Alexandra Mullins and colleagues from the Waters Group, report the first synthetic receptor capable of selectively recognizing asymmetric dimethylarginine, Rme2a. This was achieved by using a biased dynamic combinatorial chemistry, DCC, library to generate a receptor mimicking the 5‐sided box‐like shape of Rme2 reader proteins, a feature that has been hypothesized to impart selectivity. Additionally, the group members synthesized a thioether‐linked analogue of the resulting receptor to provide a novel scaffold with maintained selectivity but greater stability.

This work, which after publication has been designated a "Hot Paper" by the publishers of Angewandte Chemie, introduces strategies that can be applied towards achieving selectivity based on subtle differences in hydrophilic guests in aqueous solutions.