A Brief Overview of Recent Advances in the Applications of Boro nic Acids Relevant to Glycomics

Abstract

BOH) have been utilised in a wide range of applications, including as reaction promoters and catalysts [1-4] as dyes,[5] as support for derivatisation and affinity purification of diols, sugars and glycosylated proteins,[6] as sensors for carbohydrates,[7-8] as protecting or activating groups in carbohydrate synthesis,[9-12] as separation or membrane transport tools,[13-15] and as a pharmacophore in medicinal chemistry.[16-17] Here, the authors would like to focus on the most recent advances (mainly the past 5 years) in the applications of boronic acids important to the “glycosciences” and related fields.Fluorescence-based saccharide sensing using boronic acid-based entities has been investigated for nearly 25 years[18-21] because it is recognized that boronic acids have the potential to afford semi-invasive or non-invasive monitoring of carbohydrate levels in a variety of medical conditions, including cancer and diabetes. Glucose-level monitoring is of paramount importance to limit the long-term consequences of diabetes mellitus (e.g. damage to the heart, eyes, kidneys, nerves and other organs caused by malign glycation of vital protein structures). [22] A number of challenges still require improvement, including increased discrimination between monosaccharides, functioning under physiological conditions and sensor stability towards photobleaching or oxidation. [23,24] The relative binding constants (K) of monosaccharides with boronic acids reveal glucose to be a weak boronic acid binder,[25] and D-fructose a strong binder which presents a problem in the development of glucose-selective artificial receptors. This issue has been partially ameliorated by the utilization of diboronates. However, these bulkier sensors tend to be less water soluble than their monoboronate counterparts. [23-24] Increasing the sensor’s water solubility profile, whilst still retaining the low pKa values for binding at neutral pH, has been achieved by introduction of a pyridiniumboronic acid unit in the sensor molecule [26-27].Recent advances in this field include the bisanthracene diboronic acids (e.g. 1, figure 1) developed by Wang and co-workers,[28] which showed that the careful balance of orientation and distance between the two boronic acids results in sensors, such as 2, that can bind selectively to D-glucose over D-fructose (K = 1472 M