Figure 2.
Boronic acid mediated dynamic conjugation of aryl aldehydes and ketones with biological amines. (a) Schematic comparison of aryl aldehydes/ketones with and without the ortho-boronic acid substituent in their conjugation reaction with primary amines. The much reduced Kd values highlights the superior thermodynamic stability of iminoboronates. (b) Reversible covalent labeling of gram-positive bacteria enabled by the iminoboronate formation of Lys-PG that synergizes with electrostatic interactions. (c) Reversible covalent inhibition of Mcl-1 achieved by installing the 2-APBA warhead onto a noncovalent ligand of the target protein. The inhibitor structure is shown on the left and a structural model of the inhibitor-protein complex is shown on the right with the iminoboronate-forming Lys residue highlighted (details can be found in ref. 16).