An Improved Class of Sugar-Binding Boronic Acids, Soluble and Capable of Complexing Glycosides in Neutral Water

Abstract

This study describes a new class of carbohydrate-binding boronic acids. ortho-Hydroxymethyl phenylboronic acid (boronophthalide) was shown to be superior to the well-established dialkylamino ("Wulff-type") analogues, and it is more soluble in aqueous solvents. The most significant finding in this work is the surprising ability of ortho-hydroxyalkyl arylboronic acids to complex model glycopyranosides under physiologically relevant conditions. These boronic acid units appear to complex hexopyranosides mainly using their 4,6-diol. This behavior is significant because a majority of cell-surface glycoconjugates present free 4,6-diols. Thus, conjugatable forms of these boronic acids could be used in the design of oligomeric receptors and sensors to exploit multivalency effects. Such receptors could dramatically expand the potential of boronic acids toward the selective recognition of cell-surface glycoconjugates.

Boron-Carbohydrate Interactions

“…The Hall group has provided an important solution to this problem when they showed that benzoboroxoles can bind methyl hexopyranosides in water at pH 7.5. [37] For glucopyranosides, the only significant binding site is the C-4/C-6 diol as all vicinal diols in this system are of a trans relationship. In galactopyranosides, there is an additional possible binding site: the C-3/C-4 cis-diol ( Figure 7): While a significant amount of research has been dedicated to the study of boronatemonosaccharide interactions, very little has been invested in borinate-monosaccharide exchange.…”

Expanding Roles for Organoboron Compounds – Versatile and Valuable Molecules for Synthetic, Biological and Medicinal Chemistry

“…Given the importance of glucose monitoring for patients with diabetes and for other applications, a great amount of effort has been directed towards the development of boronic acid-containing sensors that can operate under physiological conditions for routine monitoring. [56,57] Alternative applications of these boronic acid glucose sensors involve glucose imaging, and the use of novel polymeric materials that can be used for the controlled release of insulin on binding of glucose. [37] Finally, fluorescent boronic acid sensors can be used in a diagnostic manner for the detection and labelling of fucosylated oligosaccharides that occur in surface carbohydrates that are common in certain cancers.…”

Investigation of Selective Recognition of Sugars Using Lectin-inspired Temperature-responsive Polymers

“…17 Recently, Hall and co-workers found that benzoxaborole groups showed a higher affinity than boronic acid toward saccharides at physiological pH as it has a physiologically suitable pK a of 7.2. 18,19 We have recently reported the successful preparation of benzoxaborole-containing polymers and demonstrated their specific interaction with glycolpolymers under various conditions. 20,21 In this study, we investigated selective sugar recognition of benzoxaborole-containing polymers using different monoand disaccharides.…”