CHLin 2013

Development of fucosyltransferase and fucosidase inhibitors

L-Fucose-containing glycoconjugates play an indispensible role in a myriad of physiological and pathological activities, such as inflammation, bacterial and viral infections, tumor metastasis and genetic disorders.

Fucosyltransferases (FucTs) and fucosidases, the main enzymes involved in the incorporation and cleavage of L-fucose residues, respectively, represent captivating targets for therapeutic treatment and diagnosis. FucTs are classified into .-1,2-, .-1,3/4-, .-1,6- and O-FucTs according to the type of glycosidic linkages formed in the enzyme reactions. Each FucT has its unique substrate specificity. In addition, there are two .-L-fucosidases in human that are known to have different cellular locations and activities. Their biological significances make these enzymes attractive targets for drug discovery.

To demonstrate how the synthesized small molecules interact with the target enzymes, i.e. delineation of structure–activity relationships, we cover the reaction mechanisms and resolved X-ray crystal structures, discuss how this information guides the design of enzyme inhibitors, and explain how the molecules were optimized to achieve satisfying potency and selectivity.

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Authors : Tu Z, Lin YN, Lin CH

Updated : 2013.08.22

hans 20131