Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

Xuequan Lu; Huaning Zhang; Peter J. Tonge; Derek S. Tan

doi:10.1016/j.bmcl.2008.07.130

Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

Xuequan Lu
, Huaning Zhang
, Peter J. Tonge
, Derek S. Tan

Stony Brook University

Memorial Sloan-Kettering Cancer Center
Stony Brook University

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

68 Scopus citations

Abstract

Menaquinone (vitamin K₂) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC₅₀ value of 5.7 μM.

Original language	English
Pages (from-to)	5963-5966
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2008.07.130
State	Published - Nov 15 2008

Keywords

Acyl-CoA synthetase
Antibiotic
Mechanism-based inhibitor
Mycobacterium tuberculosis
Staphylococcus aureus

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10.1016/j.bmcl.2008.07.130

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title = "Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis",

abstract = "Menaquinone (vitamin K2) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC50 value of 5.7 μM.",

keywords = "Acyl-CoA synthetase, Antibiotic, Mechanism-based inhibitor, Mycobacterium tuberculosis, Staphylococcus aureus",

author = "Xuequan Lu and Huaning Zhang and Tonge, \{Peter J.\} and Tan, \{Derek S.\}",

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doi = "10.1016/j.bmcl.2008.07.130",

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T1 - Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

AU - Lu, Xuequan

AU - Zhang, Huaning

AU - Tonge, Peter J.

AU - Tan, Derek S.

PY - 2008/11/15

Y1 - 2008/11/15

N2 - Menaquinone (vitamin K2) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC50 value of 5.7 μM.

AB - Menaquinone (vitamin K2) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC50 value of 5.7 μM.

KW - Acyl-CoA synthetase

KW - Antibiotic

KW - Mechanism-based inhibitor

KW - Mycobacterium tuberculosis

KW - Staphylococcus aureus

UR - https://www.scopus.com/pages/publications/55249100482

U2 - 10.1016/j.bmcl.2008.07.130

DO - 10.1016/j.bmcl.2008.07.130

M3 - Article

C2 - 18762421

SN - 0960-894X

VL - 18

SP - 5963

EP - 5966

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 22

ER -

Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

Abstract

Keywords

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