The First Fluorescent Diboronic Acid Sensor Specific for Hepatocellular Carcinoma Cells Expressing Sialyl Lewis X

Abstract

Carbohydrate antigens with subterminal fucosylation have been implicated in the development and progression of several cancers, including hepatocellular carcinoma (HCC). Fluorescent sensors targeting fucosylated carbohydrate antigens could potentially be used for diagnostic and other applications. We have designed and synthesized a series of 26 diboronic acid compounds as potential fluorescent sensors for such carbohydrates. Among these compounds, 7q was able to fluorescently label cells expressing high levels of sLex (HEPG2) within a concentration range of 0.5 to 10 microM. This compound (7q) did not label cells expressing Lewis Y (HEP3B), nor cells without fucosylated antigens (COS7). This represents the first example of a fluorescent compound labeling cells based on cell surface carbohydrate structures.

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

“…[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. [58] …”

Boron-Carbohydrate Interactions

“…[28] In 2002, Weston and Wang reported the ability to target a specific oligosaccharide epitope of a cell surface glycoconjugate. [60,61] Use of a fluorescent bis-boronate to label the cancerrelated antigen sialyl Lewis X on hepatocellular carcinoma cells was an important achievement. They used a combinatorial approach to optimize a bis-boronate in targeting the sialic acid and fucose residues on the tetrasaccharide.…”

Methyl 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-nitrobenzoate

“…For a review on borolectins, see : Yang et al (2002: Yang et al ( , 2004. For the utilization of boronic acids as enzyme inhibitors, see: Adams et al (1998);Fevig et al (1996); Johnson & Houston (2002); Kettner et al (1990); Prusoff et al (1993).…”

“…However, they have found wider applications more recently as sensors of 'gallate-like′ compounds in the alcoholic beverage industry (Wiskur & Anslyn, 2001), in the development of saccharide sensors (in vivo at neutral pH in aqueous environment) (Baxter et al, 1990;Fedorak et al, 1989;Yamamoto et al, 1990;Yasuda et al, 1990), boronolectins (Yang et al, 2002(Yang et al, , 2004, as protease (Fevig et al, 1996;Kettner et al, 1990;Prusoff et al, 1993), glycosidase (Johnson & Houston, 2002) and proteasome inhibitors (Adams et al, 1998).…”