Rapid ligations with equimolar reactants in water with the potassium acyltrifluoroborate (KAT) amide formation

Abstract

The identification of fast, chemoselective bond-forming reactions is one of the major contemporary challenges in chemistry. We show that chemoselective amide-forming ligations of potassium acyltrifluoroborates (KATs) and O-carbamoylhydroxylamines proceed in the presence of all unprotected functional groups with a second-order rate constant of 20 M-1 s-1. PEG chains, lipids, biotin, and dyes were introduced onto an unprotected 31-mer peptide (a GLP-1 analogue) with equimolar ratios of reactants within minutes at 1 mM and within 1 h at 100 μM, even with Mw 20 000 PEG. This conjugation reaction provides a new approach to the synthesis of molecules such as protein-protein and protein-polymer conjugates. © 2014 American Chemical Society.