Abstract
Synthesis of bisubstrate type inhibitor for N-acetylglucosaminyltransferases (GnTs), which are involved in cancer metastasis and neuronal development, was achieved. It utilized polymer resin hybrid capture–release strategy for the construction of the acceptor trisaccharide component, which was employed low molecular weight PEG and cysteine loading resin. Bromoacetamide having GlcNAc phosphate derivative was synthesized independently as a donor component. Chemoselective ligation procedure was applied for the selective coupling between donor and thiol induced acceptor component in aqueous media. After SepPakTM C-18 purification based on hydrophobic tag, it was converted to the target compound using UMP-morpholidate for the instruction of UDP component. Inhibitory activities toward GnT-V and IX were evaluated to reveal its potency toward the latter enzyme (Ki = 7.2 μM).
