Rational design of inhibitors of VirA-VirG two-component signal transduction

Justin Maresh; Jin Zhang; Yih Ling Tzeng; Nora A. Goodman; David G. Lynn

doi:10.1016/j.bmcl.2007.04.018

Rational design of inhibitors of VirA-VirG two-component signal transduction

Justin Maresh, Jin Zhang, Yih Ling Tzeng, Nora A. Goodman, David G. Lynn

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

9 Scopus citations

Abstract

VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium.

Original language	English (US)
Pages (from-to)	3281-3286
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2007.04.018
State	Published - Jun 15 2007
Externally published	Yes

Keywords

Agrobacterium
Benzoxazinone
Pathogenesis
Therapeutics
Two-component signaling
Virulence

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmcl.2007.04.018

Cite this

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title = "Rational design of inhibitors of VirA-VirG two-component signal transduction",

abstract = "VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium.",

keywords = "Agrobacterium, Benzoxazinone, Pathogenesis, Therapeutics, Two-component signaling, Virulence",

author = "Justin Maresh and Jin Zhang and Tzeng, {Yih Ling} and Goodman, {Nora A.} and Lynn, {David G.}",

year = "2007",

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doi = "10.1016/j.bmcl.2007.04.018",

language = "English (US)",

volume = "17",

pages = "3281--3286",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Rational design of inhibitors of VirA-VirG two-component signal transduction

AU - Maresh, Justin

AU - Zhang, Jin

AU - Tzeng, Yih Ling

AU - Goodman, Nora A.

AU - Lynn, David G.

PY - 2007/6/15

Y1 - 2007/6/15

N2 - VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium.

AB - VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium.

KW - Agrobacterium

KW - Benzoxazinone

KW - Pathogenesis

KW - Therapeutics

KW - Two-component signaling

KW - Virulence

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Rational design of inhibitors of VirA-VirG two-component signal transduction

Abstract

Keywords

ASJC Scopus subject areas

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