Iminoboronates as Dual-Purpose Linkers in Chemical Probe Development

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. a-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 aamino hydrazide provides further modification, for example to introduce a fluorophore.

Automated summary

Chemical probes that covalently modify proteins are powerful tools for biological research. Choosing the right reactive group for the design of a probe is crucial, and a modular approach has been developed in this study for easy coupling of reactive groups to ligands. The iminoboronate probes synthesized in this study selectively label target proteins and can be further modified using transimination reactions with aminohydrazides, for example, to introduce fluorophores.