Triazole-linked fluorescent bisboronic acid capable of selective recognition of the Lewis Y antigen

Abstract

Cell surface carbohydrates of the Lewis blood group antigens, Lewis X (Le), Lewis Y (Le), Lewis A (Le), and their sialylated derivatives, such as sialy Lewis X (sLe) and sialy Lewis A (sLe), play important roles in various recognition processes. These cell surface carbohydrates have also been associated with the development and progression of many types of cancers. Recently, we synthesized four anthracene-based fluorescent bisboronic acid sensors (compounds 2a-d) linked by 'click' chemistry with tethers of different lengths to match the epitope of various Lewis group of sugars. Among the four compounds, 2a appears to have both high sensitivity and selectivity for Le among other carbohydrate antigens.

Recent development of boronic acid-based fluorescent sensors

“…80 It was found that the uorescence of 30a increased aer binding to sialyl Lewis Y. The result indicates that 30a has a high sensitivity and selectivity for sialyl Lewis Y.…”

“…Wang et al synthesized four anthracene-based fluorescent diboronic acid sensors (30a–d) and examined the selectivity of different length linkers for sialyl Lewis. 80 It was found that the fluorescence of 30a increased after binding to sialyl Lewis Y. The result indicates that 30a has a high sensitivity and selectivity for sialyl Lewis Y.…”

Molecular Boronic Acid-Based Saccharide Sensors

“…Also harnessing the power of click chemistry, in 2017 Wang et al produced a series of four fluorescent bis-boronic acids targeting the Lewis group of cell-surface tetrasaccharides, 37a – d , Figure . In essence, two of the Shinkai and co-workers’ PBA-anthracene-type systems are appended with different linker lengths and are “clicked” together about a triazole core.…”

Targeting extracellular glycans: tuning multimeric boronic acids for pathogen-selective killing of Mycobacterium tuberculosis

“…Compound 7 , with a longer linker (∼10 nm) was ineffective, with higher MICs and loss of specificity for mycobacteria. Multivalent presentation of boronic acids has been reported to lead to increased binding affinities,22 and the nature and length of the linker has been demonstrated in other studies to have a large influence on boronic acid binding selectivity and affinity and is likely to be important here 23. The increased activity of the shorter linkers would support a chelation mechanism to the cell glycans (see below for experimental evidence of binding).…”