The Design and Evaluation of Boronic Acid Derivatives for the Recognition of Cell Surface Carbohydrates for Medicinal Applications

Carbohydrates in various forms play vital roles in numerous critical biological processes including cell-cell adhesion and communication, embryo development, immune response, etc. Fluorescent sensors for such carbohydrates have a wide range of potential applications including glucose concentration determination, cell labeling and targeting based on carbohydrate biomarkers, as in vitro diagnostic tools, and biomarker-directed cellular imaging. Our group has been interested in the design and synthesis of multi-boronic acid compounds with well-defined three-dimensional scaffolding for the specific recognition of selected carbohydrate biomarkers. Aberrant expression of carbohydrate antigens such as sialyl Lewis X (sLex), sialyl Lewis A (sLea), Lewis X (Lex), and Lewis Y (Ley) have been associated with tumor formation and metastasis in various cancer types. As such, for our initial design, we have selected sialyl Lewis X (sLex) as our potential target due to implication in the development of liver and colon cancer. 5, 6 Herein, we describe the design, synthesis and evaluation of four such compounds, each having about ten linear steps in its synthesis. In addition to the design of fluorescent probes for cell surface carbohydrates, we also have designed lipophilic boronic acid derivatives as potential fusogenic agents. Due to boronic acid's ability to bind to 1,2 and 1,3 cis diols, we hypothesize that the aliphatic chain should be able to insert into lipid cellular membrane and the boronic acid units should allow for the " attachment to neighboring cells " through complexation with cell surface glycans. Such interactions should allow the boronic acid compounds to bring two or more cells together for fusion. Herein, we have described the methodologies of the design of such compounds. Once I reflected on everything that was good and wanted to thank him for all his creations. Kneeling suddenly appeared this revelation. I envisioned His hands reaching down on a ball of clay molding and shaping a man in just one day. He reveled at the finished product and knew this accomplishment was grand, But wanted to add perfection to his great land and decided to create woman. An easy task he knew this would not be for this creature would reign as Queen and from her would be born all posterity. The Creator took his time and shaped a form that was sophisticated and added loyalty for she was going to be dedicated. He made her audacious and autonomous to convey her strength. Delightful, admirable, graceful so her company will be …