Chemoenzymatic synthesis of GDP-L-fucose derivatives as potent and selective α-1,3-fucosyltransferase inhibitors

Yu Nong Lin, Daniel Stein, Sheng Wei Lin, Sue Ming Chang, Ting Chien Lin, Yu Ruei Chuang, Jacquelyn Gervay-Hague, Hisashi Narimatsu, Chun Hung Lin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Fucosyltransferases (FucTs) usually catalyze the final step of glycosylation and are critical to many biological processes. High levels of specific FucT activities are often associated with various cancers. Here we report the development of a chemoenzymatic method for synthesizing a library of guanosine diphosphate β-L-fucose (GDP-Fuc) derivatives, followed by in situ screening for inhibitory activity against bacterial and human α-1,3-FucTs. Several compounds incorporating appropriate hydrophobic moieties were identified from the initial screening. These were individually synthesized, purified and characterized in detail for their inhibition kinetics. Compound 5 had a K i of 29 nM for human FucT-VI, and is 269 and 11 times more selective than for Helicobacter pylori FucT (K i=7.8 μM) and for human FucT-V (K i=0.31 μM).

Original languageEnglish (US)
Pages (from-to)1750-1758
Number of pages9
JournalAdvanced Synthesis and Catalysis
Issue number9
StatePublished - Jun 18 2012


  • enzyme catalysis
  • enzymes
  • guanosine diphosphate β- L -fucose (GDP-Fuc) derivatives
  • inhibitors
  • transferases

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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