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 S. Burgos, Laurent Salmon

Research output: Contribution to journalArticle

8 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Arabinose
Kinetics
Enzyme Inhibitors
Isomerization
Phosphates
ribosephosphate isomerase
ribulose 5-phosphate
ribose-5-phosphate

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

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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.",
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T1 - Synthesis and kinetic evaluation of 4-deoxy-4-phosphonomethyl-D- erythronate, the first hydrolytically stable and potent competitive inhibitor of ribose-5-phosphate isomerase

AU - Burgos, Emmanuel S.

AU - Salmon, Laurent

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Y1 - 2004/4/19

N2 - 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.

AB - 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.

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KW - Phosphonate

KW - Ribose-5-phosphate isomerase

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