RESUMEN
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.
Asunto(s)
Ácidos Borónicos/química , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Oligosacáridos/análisis , Oligosacáridos/genética , Animales , Ácidos Borónicos/síntesis química , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Línea Celular , Fluorescencia , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Estructura Molecular , Oligosacáridos/química , Antígeno Sialil Lewis XRESUMEN
A series of fluorescent diboronic acids was synthesized in nine steps as potential sensors for sialyl Lewis X (sLex). The fluorescent binding studies of these sensors with sLex were carried out in a mixed aqueous solution. Compound 7e was found to show the strongest fluorescence enhancement upon binding with sLex. Using cell cultures, 7e was shown to label sLex-expressing HEPG2 cells at 1 microM, while non-sLex-expressing cells were not labeled.