# Peptide Boronic Acids by Late‐Stage Hydroboration on the Solid Phase

## TL;DR

This paper introduces a new method to create peptide boronic acids using hydroboration on solid-phase, enabling shorter linkers and potential applications in drug discovery and diagnostics.

## Contribution

A novel on-resin hydroboration method for synthesizing peptide boronic acids with regio- and stereoselectivity.

## Key findings

- Peptide boronic acids with shorter linkers were successfully synthesized using transition metal-catalyzed hydroboration.
- The method is compatible with all canonical amino acid residues and works on various peptide sequences.
- Peptide boronic acids demonstrated reversible binding to carbohydrates in a model experiment.

## Abstract

Organoboron compounds have a wide range of applications in numerous research fields, and methods to incorporate them in biomolecules are much sought after. Here, on‐resin chemical syntheses of aliphatic and vinylogous peptide boronic acids are presented by transition metal‐catalyzed late‐stage hydroboration of alkene and alkyne groups in peptides and peptoids, for example on allyl‐ and propargylglycine residues, using readily available chemicals. These methods yield peptide boronic acids with much shorter linkers than previously reported on‐resin methods. Furthermore, the methods are regio‐ and stereoselective, compatible with all canonical amino acid residues and can be applied to short, long, and in part even “difficult” peptide sequences. In a feasibility study, the protected peptide vinylboronic acids are further derivatized by the Petasis reaction using salicylaldehyde derivatives. The ability of the obtained peptide boronic acids to reversibly bind to carbohydrates is demonstrated in a catch‐release model experiment using a fluorescently labeled peptide boronic acid on cross‐linked dextran beads. In summary, this highlights the potential of the target compounds for drug discovery, glycan‐specific target recognition, controlled release, and diagnostics.

Transition metal‐catalyzed hydroboration of peptide alkenes and alkynes with readily available reactants selectively yields aliphatic‐ and vinylboronic acids in a straightforward, on‐resin, late‐stage functionalization approach. Reversible binding of the obtained peptide boronic acids to carbohydrates and further functionalization by Petasis reaction is also demonstrated.