IngentaConnect Carbohydrate-Based Mimics of D-myo-Inositol 1,4,5-Trisphosphate

Authors: Chretien F.; Moitessier N.; Roussel F.; Mauger J.; Chapleur Y.

Source: Current Organic Chemistry, Volume 4, Number 5, May 2000 , pp. 513-534(22)

Publisher: Bentham Science Publishers

Abstract:

Many cellular events such as secretion or proliferation require activation of proteins by calcium ions. Intracellular calcium is mobilized by the formation of the second messenger D-myo-inositol 1,4,5-trisphosphate (InsP3) and subsequent binding to a receptor located on the endoplasmic reticulum. Pharmacological studies of these biological processes have stimulated the search for new ligands of the InsP3 receptor (InsP3R) able to promote or to block the calcium-signaling pathway. As a result, many analogs of InsP3 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 InsP3R have been disclosed but a synthetic antagonist of InsP3R yet to be discovered. One disadvantage of the use of inositol as starting material is its meso structure and the number of protecting groups manipulation needed to put in place the appropriate phosphate decoration. Some years ago, we reasoned that carbohydrates might be used as scaffolds mimicking the inositol ring to properly present the trisphosphate pattern. During the course of our preliminary investigations the discovery of the adenophostins shed light on a new way to design highly potent calcium mobilizing agents. This review will summarize on advances in the field of the use of carbohydrates as surrogates for inositol and the use of adenophostins as a model.

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