Iminoboronates as Dual-Purpose Linkers in Chemical Probe Development

Chemistry. 2021 Feb 15;27(10):3292-3296. doi: 10.1002/chem.202005115. Epub 2021 Jan 14.

Abstract

Chemical probes that covalently modify proteins of interest are powerful tools for the research of biological processes. Important in the design of a probe is the choice of reactive group that forms the covalent bond, as it decides the success of a probe. However, choosing the right reactive group is not a simple feat and methodologies for expedient screening of different groups are needed. We herein report a modular approach that allows easy coupling of a reactive group to a ligand. α-Nucleophile ligands are combined with 2-formylphenylboronic acid derived reactive groups to form iminoboronate probes that selectively label their target proteins. A transimination reaction on the labeled proteins with an α-amino hydrazide provides further modification, for example to introduce a fluorophore.

Keywords: affinity-based probes; bio-orthogonal chemistry; chemical probes; iminoboronate; protein labeling.