Tetrafluorination of sugars as strategy for enhancing protein-carbohydrate affinity: Application to UDP-galp mutase inhibition

Inès N'Go, Samuel Golten, Ana Ardá, Javier Cañada, Jesús Jiménez-Barbero, Bruno Linclau, Stéphane P. Vincent

Research output: Contribution to journalArticle

Abstract

Tetrafluorinated analogues of both UDP-galactopyranose and UDP-galactofuranose have been synthesized and assayed against UDP-galactopyranose mutase, a key enzyme for Mycobacterium tuberculosis cell wall biosynthesis. Competition assays and STD-NMR spectroscopy techniques have evidenced not only the first unambiguous case of affinity enhancement through local sugar polyfluorination, but also showed that tetrafluorination can still have a beneficial effect on binding when monofluorination at the same position does not. On all fours: Tetrafluorinated analogues of UDP-galactopyranose and UDP-galactofuranose were synthesized and assayed against UDP-galactopyranose mutase (UGM), a key enzyme in Mycobacterium tuberculosis cell wall biosynthesis. The tetrafluorinated sugar analogue was found to bind the enzyme more effectively than the unfluorinated natural substrate.

Original languageEnglish
Pages (from-to)106-12
Number of pages7
JournalChemistry: A European Journal
Volume20
Issue number1
DOIs
Publication statusPublished - 2014

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Keywords

  • carbohydrates
  • fluorine
  • inhibitors
  • NMR spectroscopy
  • tuberculosis

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