Organic chemistry

Combinatorial chemistry

Hydroxylamine

Chemistry

Boronic acid

Click chemistry

Bioorthogonal chemistry

Angewandte Chemie International Edition

Over the past two decades, bioorthogonal chemistry has become a preferred tool to achieve site-selective modifications of proteins. However, there are only a handful of commonly applied bioorthogonal reactions and they display some limitations, such as slow rates, use of unstable or cytotoxic reagents, and side reactions. Hence, there is significant interest in expanding the bioorthogonal chemistry toolbox. In this regard, boronic acids have recently been introduced in bioorthogonal chemistry and are exploited in three different strategies: 1) boronic ester formation between a boronic acid and a 1,2-cis diol; 2) iminoboronate formation between 2-acetyl/formyl-arylboronic acids and hydrazine/hydroxylamine/semicarbazide derivatives; 3) use of boronic acids as transient groups in a Suzuki-Miyaura cross-coupling or other reactions that leave the boronyl group off the conjugation product. In this Review, we summarize progress made in the use of boronic acids in bioorthogonal chemistry to enable site-selective labeling of proteins and compare these methods with the most commonly utilized bioorthogonal reactions.

Boronic Acids as Bioorthogonal Probes for Site‐Selective Labeling of Proteins