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

doi:10.1016/j.tetlet.2004.03.004

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

Biochemistry

Research output: Contribution to journal › Article › peer-review

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 (K_i=74μM, K _m/K_i=100), exhibiting only a 3-fold weaker inhibitory activity than its phosphate analogue.

Original language	English (US)
Pages (from-to)	3465-3469
Number of pages	5
Journal	Tetrahedron Letters
Volume	45
Issue number	17
DOIs	https://doi.org/10.1016/j.tetlet.2004.03.004
State	Published - Apr 19 2004

Keywords

Enzyme inhibitor
Phosphonate
Ribose-5-phosphate isomerase

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tetlet.2004.03.004

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

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.",

keywords = "Enzyme inhibitor, Phosphonate, Ribose-5-phosphate isomerase",

author = "Emmanuel Burgos and Laurent Salmon",

note = "Funding Information: The Minist{\`e}re de l'Education Nationale et de la Recherche (E.B.) is gratefully acknowledged for financial support (2001–2004).",

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doi = "10.1016/j.tetlet.2004.03.004",

language = "English (US)",

volume = "45",

pages = "3465--3469",

journal = "Tetrahedron Letters",

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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

AU - Salmon, Laurent

N1 - Funding Information: The Ministère de l'Education Nationale et de la Recherche (E.B.) is gratefully acknowledged for financial support (2001–2004).

PY - 2004/4/19

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.

KW - Enzyme inhibitor

KW - Phosphonate

KW - Ribose-5-phosphate isomerase

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U2 - 10.1016/j.tetlet.2004.03.004

DO - 10.1016/j.tetlet.2004.03.004

M3 - Article

AN - SCOPUS:1842637289

SN - 0040-4039

VL - 45

SP - 3465

EP - 3469

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 17

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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