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.
Izumi
Masayuki
M
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
Kaneko
Syunsuke
S
Yuasa
Hideya
H
Hashimoto
Hironobu
H
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