Exploring a multivalent approach to α-L-fucosidase inhibition

Elena Moreno-Clavijo, Ana T. Carmona, Antonio J. Moreno-Vargas, Lidia Molina, Daniel W. Wright, Gideon J. Davies, Inmaculada Robina*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the 3E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.

Original languageEnglish
Pages (from-to)7328-7336
Number of pages9
JournalEuropean Journal of Organic Chemistry
Issue number32
Early online date19 Sep 2013
DOIs
Publication statusPublished - 10 Oct 2013

Keywords

  • Carbohydrates
  • Enzymes
  • Glycoconjugates
  • Imino sugars
  • Inhibitors
  • Structure-activity relationships

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