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

Research output: Contribution to journalArticle

412 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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galactoside 3-fucosyltransferase
Click Chemistry
Fucosyltransferases
Cycloaddition
Acetylene
Screening
Glycosyltransferases
Molecules
Triazoles
Azides
Cycloaddition Reaction
Substrates
Hydrophobic and Hydrophilic Interactions

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

A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry. / Lee, Lac V.; Mitchell, Michael L.; Huang, Shih Jung; Fokin, Valery V.; Sharpless, K. Barry; Wong, Chi Huey.

In: Journal of the American Chemical Society, Vol. 125, No. 32, 13.08.2003, p. 9588-9589.

Research output: Contribution to journalArticle

Lee, LV, Mitchell, ML, Huang, SJ, Fokin, VV, Sharpless, KB & Wong, CH 2003, 'A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry', Journal of the American Chemical Society, vol. 125, no. 32, pp. 9588-9589. https://doi.org/10.1021/ja0302836
Lee, Lac V. ; Mitchell, Michael L. ; Huang, Shih Jung ; Fokin, Valery V. ; Sharpless, K. Barry ; Wong, Chi Huey. / A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry. In: Journal of the American Chemical Society. 2003 ; Vol. 125, No. 32. pp. 9588-9589.
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