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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Hydroxamic Acids
Isomerases
Spinacia oleracea
Enzyme Inhibitors
Mycobacterium tuberculosis
Phosphates
Acids
Enzymes
allose
Lead
neurotensin mimic 2
ribosephosphate isomerase
erythronohydroxamic acid
neurotensin mimic 1

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

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

In: Tetrahedron Letters, Vol. 46, No. 21, 23.05.2005, p. 3691-3694.

Research output: Contribution to journalArticle

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