Synthesis and kinetic evaluation of 4-deoxy-4-phosphonomethyl-D- erythronate, the first hydrolytically stable and potent competitive inhibitor of ribose-5-phosphate isomerase

Emmanuel Burgos, Laurent Salmon

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

4-deoxy-4-Phosphonomethyl-D-erythronate, an isosteric and hydrolytically stable analogue of the known ribose-5-phosphate isomerase inhibitor 4-deoxy-4-phospho-D-erythronate, was obtained by a 14-step synthesis from D-arabinose through an highly improved synthesis of the precursor 5-deoxy-5-phosphonomethyl-D-arabinose. The title compound appears as the first stable and potent competitive inhibitor of the enzyme catalyzed isomerization of ribose-5-phosphate to D-ribulose-5-phosphate (Ki=74μM, K m/Ki=100), exhibiting only a 3-fold weaker inhibitory activity than its phosphate analogue.

Original languageEnglish (US)
Pages (from-to)3465-3469
Number of pages5
JournalTetrahedron Letters
Volume45
Issue number17
DOIs
StatePublished - Apr 19 2004

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Keywords

  • Enzyme inhibitor
  • Phosphonate
  • Ribose-5-phosphate isomerase

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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