Carbohydrate sulfotransferases: novel therapeutic targets for inflammation, viral infection and cancer.
Effective direct inhibition of adhesion receptors by small molecules has been hampered by extended receptor-ligand interfaces as well as the entropic penalties often associated with inhibition of cell adhesion. Therefore, alternative strategies have targeted enzymes that are centrally involved in the biosynthesis of recognition epitopes, which are crucial for productive adhesion. Two classes of enzymes shown to play a pivotal role in cell-cell and cell-matrix adhesions are the protein-tyrosine and carbohydrate sulfotransferases, which impart crucial sulfate moieties onto glycoproteins. The carbohydrate sulfotransferases will be discussed in terms of target validation and small-molecule inhibitor discovery.
Hemmerich
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Department of Respiratory Diseases, Roche Bioscience 3401 Hillview Avenue, CA 94304, Palo Alto, USA