Synthesis of bisubstrate analogues targeting alpha-1,3-fucosyltransferase and their activities.
We designed two bisubstrate analogues targeting alpha-1,3-fucosyltransferases, based on the three dimensional structure of Lewis X, which is the product of a alpha-1,3-fucosyltransferase reaction. We selected guanosine-5'-diphospho-L-galactose as a donor mimic and 2-hydroxyethyl beta-D-galactoside as an acceptor mimic, and tethered these two mimics with a methylene or ethylene linker. For the synthesis, the 6-position of L-galactose and the 6-position of D-galactose were first tethered via a methylene or ethylene linker. The L-galactose moiety was then converted to a GDP derivative. Both bisubstrate analogues were moderate inhibitors against alpha-1,3-fucosyltransferase V and VI. The fact that they were substrates of alpha-1,3-fucosyltransferase VI suggested that these compounds bound to the donor binding site, but not to the acceptor binding site.
Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midiori-ku, Yokohama, 226-8501, Japan. masayuki.izumi@aist.go.jp
Masayuki
M
Izumi
Syunsuke
S
Kaneko
Hideya
H
Yuasa
Hironobu
H
Hashimoto
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D005647:Fucosyltransferases / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D013379:Substrate Specificity
D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase