Synthesis and evaluation of potential inhibitors of human and Escherichia coli histidine triad nucleotide binding proteins

Sanaa K. Bardaweel, Brahma Ghosh, Carston R Wagner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Based on recent substrate specificity studies, a series of ribonucleotide based esters and carbamates were synthesized and screened as inhibitors of the phosphoramidases and acyl-AMP hydrolases, Escherichia coli Histidine Triad Nucleotide Binding Protein (ecHinT) and human Histidine Triad Nucleotide Binding Protein 1 (hHint1). Using our established phosphoramidase assay, K i values were determined. All compounds exhibited non-competitive inhibition profiles. The carbamate based inhibitors were shown to successfully suppress the Hint1-associated phenotype in E. coli, suggesting that they are permeable intracellular inhibitors of ecHinT.

Original languageEnglish (US)
Pages (from-to)558-560
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Carbamates
Histidine
Escherichia coli
Carrier Proteins
Nucleotides
Ribonucleotides
Hydrolases
Adenosine Monophosphate
Substrate Specificity
Assays
Esters
Phenotype
Substrates
human HINT1 protein

Keywords

  • Hint1
  • Histidine triad binding protein
  • Inhibitor
  • Phosphoramidase

Cite this

Synthesis and evaluation of potential inhibitors of human and Escherichia coli histidine triad nucleotide binding proteins. / Bardaweel, Sanaa K.; Ghosh, Brahma; Wagner, Carston R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 1, 01.01.2012, p. 558-560.

Research output: Contribution to journalArticle

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