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 journalArticle

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 languageEnglish (US)
Pages (from-to)3281-3286
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

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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