title: Development of fucosyltransferase and fucosidase inhibitors.
abstract: L-Fucose-containing glycoconjugates are essential for a myriad of physiological and pathological activities, such as inflammation, bacterial and viral infections, tumor metastasis, and genetic disorders. Fucosyltransferases and fucosidases, the main enzymes involved in the incorporation and cleavage of L-fucose residues, respectively, represent captivating targets for therapeutic treatment and diagnosis. We herein review the important breakthroughs in the development of fucosyltransferase and fucosidase inhibitors. To demonstrate how the synthesized small molecules interact with the target enzymes, i.e. delineation of the structure-activity relationship, 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.
authors.affiliation: Institute of Biological Chemistry and Genomics Research Center, Academia Sinica, No.128 Academia Road Section 2, Nan-Kang, Taipei, 11529, Taiwan.
authors.forename: Zhijay
authors.initials: Z
authors.lastname: Tu
authors.forename: Yu-Nong
authors.initials: YN
authors.lastname: Lin
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009711:Nucleotides; C483525:fuconojirimycin; D017485:1-Deoxynojirimycin; D005647:Fucosyltransferases; D005644:alpha-L-Fucosidase