A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry

Lac V. Lee, Michael L. Mitchell, Shih Jung Huang, Valery V. Fokin, K. Barry Sharpless, Chi Huey Wong

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418 Citations (Scopus)

Abstract

Potent inhibitors of fucosyltransferases, and glycosyltransferases in general, have been elusive due to the inherent barriers surrounding the family of glycosyltransfer reactions. The problems of weak substrate affinity and low catalytic proficiency of fucosyltransferase was offset by recruiting additional binding features, in this case hydrophobic interactions, to produce a high affinity inhibitor, 24, with Ki = 62 nM. The molecule was identified from a GDP-triazole library of 85 compounds, which was produced by the Cu(I)-catalyzed [2 + 3] cycloaddition reaction between azide and acetylene reactants, followed by in situ screening without product isolation.

Original languageEnglish
Pages (from-to)9588-9589
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number32
DOIs
Publication statusPublished - 13 Aug 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Lee, L. V., Mitchell, M. L., Huang, S. J., Fokin, V. V., Sharpless, K. B., & Wong, C. H. (2003). A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry. Journal of the American Chemical Society, 125(32), 9588-9589. https://doi.org/10.1021/ja0302836