High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays.
A noncovalent carbohydrate microarray was used to screen for possible inhibitors to fucosyltransferases, which are critical to the synthesis of inflammation mediators like sialyl Lewis x (SLe(x)). Inhibition was followed by observation of the transferred fucose on the carbohydrate array with the lectin Tetragonolobus purpureas. Of these compounds, four inhibitors with nanomolar Ki(s) were discovered, with three of the top five inhibitors exhibiting a common architecture.
Bryan
Marian C
MC
Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Lee
Lac V
LV
Wong
Chi-Huey
CH
D000606:Amino Sugars / Q000737:chemistry; D002240:Carbohydrate Sequence; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D000070116:Lotus / Q000235:genetics; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology
D000606:Amino Sugars; D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D037121:Plant Lectins; C000458:N-acetyllactosamine; D005647:Fucosyltransferases