DESIGN, SYNTHESIS AND TESTING OF NOVEL INHIBITORS OF CELL ADHESION

摘要: The Selectin family of proteins comprises three carbohydrate binding proteins (E, P and L) involved in cell adhesion events¹. In response to inflammatory stimuli, these proteins play a crucial role in the recognition of sialyl Lewis X (sLe) and related carbohydrates present on the surface of neutrophils. Following recognition and binding the white blood cells are free to migrate to the sites of injury and infection². In pathogenic states this sequence of events can lead to pain and inflammation. Blocking the binding of sLe could potentially be of benefit in the treatment of inflammatory and autoimmune disorders such as, rheumatoid arthritis, asthma, psoriasis, IBD etc. XX A number of SAR studies have demonstrated that the key functional groups for the binding of sLe to E-selectin are the hydroxyl groups of the fucose unit and the carboxylic acid³ of the sialic acid unit. Clinical trials have been undertaken using some of these sLe analogues, however, the potency of these compounds is poor and they are largely carbohydrate in nature. There is a need, therefore, to develop compounds which are more potent and less susceptible to carbohydrate metabolism.