Boronic Acid Pairs for Sequential Bioconjugation

Abstract

Boronic acids can play diverse roles when applied in biological environments, and employing boronic acid structures in tandem could provide new tools for multifunctional probes. This Letter describes a pair of boronic acid functional groups, 2-nitro-arylboronic acid (NAB) and (E)-alkenylboronic acid (EAB), that enable sequential cross-coupling through stepwise nickel- and copper-catalyzed processes. The selective coupling of NAB groups enables the preparation of stapled peptides, protein–protein conjugates, and other bioconjugates.

Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

“…Our lab has recently reported a variety of selective bioconjugation approaches based on Chan–Lam coupling of boronic acid reagents with peptide or protein X–H bonds. 23–27 In a further orienting experiment, isolated sulfoximine peptide 1b proved to be a remarkably reactive substrate for Chan–Lam coupling mediated by Cu(OAc) 2 in methanol solvent (Fig. 1a and c).…”

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

“…In addition, Cu­(II)-catalyzed, histidine directed, backbone N–H arylation and alkenylation of proteins with boronic acids was achieved . By sequential addition of a heterobifunctional linker featuring 2-nitro-arylboronic acid and ( E )-alkenylboronic acid functionalities, orthogonal Ni­(II)-promoted cysteine arylation followed by Cu­(II)-catalyzed histidine-directed backbone N–H alkenylation was achieved . This strategy allowed heterodimeric protein–protein conjugates of T4 lysozyme and sfGFP to be generated with up to 93% conversion.…”

Selective Stepwise Arylation of Unprotected Peptides by PtIV Complexes

“…Nevertheless, these results demonstrate that the selective Pt IV arylation of peptides is compatible with the aqueous media, a general requirement for potential applications in protein bioconjugation. Because the observed selectivity results from the inherent reactivity preferences of the Pt IV complexes, identical or similar aromatic groups can be used for the different types of X−H bonds [28] . Furthermore, while the 19 F NMR tag is helpful in determining relative reactivity and selectivity of stepwise arylation, the reactions are clearly not limited to simple fluoroaromatics.…”