Probing the Interactions between Boronic Acids and cis-Diol-Containing Biomolecules by Affinity Capillary Electrophoresis

Abstract

The affinity of boronic acids to cis-diol-containing biomolecules has found wide applications in many fields, such as sensing, separation, drug delivery, and functional materials. A sound understanding of the binding interactions will greatly facilitate exquisite applications of this chemistry. Although a few analytical tools have been available for the characterization of the interactions, these techniques are associated with some apparent drawbacks, so they are only applicable to a limited range of boronic acids and cis-diol-containing biomolecules. Therefore, a widely applicable method is still greatly needed. In this work, an affinity capillary electrophoresis (ACE) method was established and validated to probe the interactions between boronic acids and cis-diol-containing biomolecules. The method was proven to be applicable to almost all types of cis-diol-containing biomolecules and boronic acids. Based on this method, a quantitative, comparative study on the interactions between 14 boronic acids that have important potentials for application with 5 typical monosaccharides of biological importance was carried out. The findings provided new insights into boronate affinity interactions, particularly the relationship between the binding strength with the molecular structures of the binding species. Besides, effects of pH and temperature on the binding strength were also investigated. This method exhibited several significant advantages, including (1) possibility of simultaneous study of multiple interactions, (2) low requirement on the purity of the binding species, (3) wide applicability, and (4) high accuracy and precision.

Boronic Acid‐Based Carbohydrate Sensing

“…Liu et al. reported the study of an affinity capillary electrophoresis (ACE) method to investigate the interactions between boronic acids and diol‐containing biomolecules . Remarkably, the method was found to be applicable to a wide range of both biomolecules and boronic acids.…”

A high boronate avidity monolithic capillary for the selective enrichment of trace glycoproteins

“…However, conventional boronate affinity materials suffer from an apparent limitation. The binding strength of boronic acids toward cis-diol-containing compounds is relatively weak, with dissociation constants (K d ) between boronic acids and sugars or glycoproteins ranging from 10 −1 to 10 −3 M [46,47]. Thus, capture of cis-diol-containing biomolecules especially glycoproteins of very low concentration by conventional boronate affinity materials is rather difficult or impossible.…”

“…Branched polyethyleneimine (PEI) was chosen as a scaffold to amplify the number of boronic acid moieties due to its flexible chains, plentiful amino groups, hydrophilic properties, easy post-modification and low cost. Meanwhile, 2,4-difluoro-3-formylphenylboronic acid (DFFPBA), which exhibited ultrahigh affinity toward cis-diol-containing compounds at neutral or medium acidic pH condition [47], was used as a ligand. Fig.…”

Boronic acid‐functionalized agarose affinity chromatography for isolation of tropomyosin in fishes

“…The high pKa value of traditional boronate affinity ligands would require an alkaline binding pH (8‐9) and therefore may result in the poor adsorption capacity and degeneration of biological samples, so some new materials with low pKa value have been developed, such as Wulff‐type boronic acid, improved Wulff‐type boronic acid, heterocyclic boronic acids, and boronate ligands with electron‐withdrawing groups . 3,5‐Difluoro‐4‐formylphenylboric acid had been proved to have high affinity at physiological pH environment, which is because the fluorine has strong electron absorption ability . Dendrimer‐assisted modification was considered to be an effective method to enhance boronate affinity .…”