Carbohydrate-based mimics of D-myo-inositol 1,4,5-trisphosphate

Many cellular events such as secretion or proliferation require activation of proteins by calcium ions. Intracellular calcium is mobilized by the form ation of the second messenger D-myo-inositol 1,4,5-trisphosphate (InsP(3)) and subsequent binding to a receptor located on the endoplasmic reticulum. Pharmacological studies of these biological processes have stimulated the s earch for new ligands of the InsP(3) receptor (InsP(3)R) able to promote or to block the calcium-signaling pathway. As a result, many analogs of InsP( 3) itself have been prepared by modification of the inositol structure and or modification of the trisphosphate pattern and have been tested for their ability to mobilize calcium. Many weak to full agonists of InsP(3)R have b een disclosed but a synthetic antagonist of InsP(3)R yet to be discovered. One disadvantage of the use of inositol as starting material is its meso st ructure and the number of protecting groups manipulation needed to put in p lace the appropriate phosphate decoration. Some years ago, we reasoned that carbohydrates might be used as scaffolds mimicking the inositol ring to pr operly present the trisphosphate pattern. During the course of our prelimin ary investigations the discovery of the adenophostins shed light on a new w ay to design highly potent calcium mobilizing agents. This review will summ arize on advances in the field of the use of carbohydrates as surrogates fo r inositol and the use of adenophostins as a model.