Synthesis of 5-deoxy-5-phospho-D-ribonohydroxamic acid: A new competitive and selective inhibitor of type B ribose-5-phosphate isomerase from Mycobacterium tuberculosis

Emmanuel Burgos, Annette K. Roos, Sherry L. Mowbray, Laurent Salmon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

5-Deoxy-5-phospho-d-ribonohydroxamic acid, a mimic of the 1,2-cis-enediolate high-energy intermediate species of the allose-6-phosphate isomerase reaction, was obtained by a six-step synthesis from d-erythronolactone. In contrast to the known competitive ribose-5-phosphate isomerase (Rpi) inhibitors 4-deoxy-4-phospho-d-erythronohydroxamic acid, 4-deoxy-4-phospho-d-erythronate, and 4-deoxy-4-phosphonomethyl-d-erythronate, the new hydroxamic acid selectively inhibits Mycobacterium tuberculosis RpiB (Ki = 0.40 mM, Km/Ki = 4.5) versus Spinacia oleracea RpiA, and hence appears as a promising lead for the design of potent species-specific inhibitors of the bacterial enzyme.

Original languageEnglish (US)
Pages (from-to)3691-3694
Number of pages4
JournalTetrahedron Letters
Volume46
Issue number21
DOIs
StatePublished - May 23 2005

Keywords

  • 5-Phosphate D-ribose isomerase
  • 6-Phosphate D-allose isomerase
  • Competitive inhibitor
  • Phosphate sugar
  • RpiB

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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