Using boronolectin in MALDI-MS imaging for the histological analysis of cancer tissue expressing the sialyl Lewis X antigen

Abstract

Certain carbohydrate-based biomarkers are known to correlate with cancer formation and progression. By targeting sialyl Lewis X, we have developed the first boronolectin-MS tag conjugate, which allows for MALDI-based imaging of cancer based on its cell surface carbohydrate.

Click with a boronic acid handle: a neighboring group-assisted click reaction that allows ready secondary functionalization

“…In doing so, we were interested in exploring the ability of a boronic acid group to function as a Lewis acid. Our lab has had a long-standing interest in boronic acid chemistry, exploring its applications in sensing, 13 catalysis, 14 drug design, 15 and imaging 16 as well as its behavior in mass spectrometry. 17 It is well known that a Lewis base/nucleophile in a 1,5-relationship with an arylboronic acid can donate its lone pair electrons to the boron open shell.…”

Probe-based chemical modulations of tissues for IMS

“…Combining boronolectin I with a triethyl-based tag they carried out a matrix-free MALDI-IMS of SLe X on renal cell carcinoma (Fig. 3) [28]. Further advantages of this approach include its excellent stability, easy storage, well-defined conjugation chemistry, and its compatibility with organic solvents in sample preparation and tissue handling.…”

“…Certain carbohydrate-based biomarkers are known to be associated with cancer formation and progression [28]. The tetrasaccharide carbohydrate that is usually attached to O-glycans on the surface of cells, Sialyl-Lewis X (SLe X ), is used as a predictive target in cancer research.…”

A fluorescent bisboronic acid compound that selectively labels cells expressing oligosaccharide Lewis X

“…15–17 Our laboratory has been particularly interested in the development of fluorescent sensors for biologically important carbohydrates. 18–21 For the construction of fluorescent sensors for cell surface carbohydrates, we envision that bisboronic acid compounds with a proper spatial arrangement of the two boronic acid moieties, which are complementary to the multiple pairs of diols, have the potential for selective recognition of the target carbohydrate. In doing so, we have selected Shinkai’s anthracene-based fluorescent boronic acid as the binding and reporting unit 22 and have sampled a series of linkers with different length, rigidity, and spatial orientation in search of an optimal arrangement of the two boronic acid units.…”

“…18–20 The same sensor was found to be useful in mass spectrometric imaging work for cancer tissues. 21 Herein, we report a fluorescent boronic acid compound ( 6a ) that selectively label Le x , which was derived from screening a large number of analogs with a range of boron-boron distance considered as appropriate for recognition of Le x . The computational aspect of this study is addressed later.…”