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

Sanaa K. Bardaweel; Brahma Ghosh; Carston R. Wagner

doi:10.1016/j.bmcl.2011.10.082

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

Sanaa K. Bardaweel, Brahma Ghosh, Carston R. Wagner

Medicinal Chemistry

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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 language	English (US)
Pages (from-to)	558-560
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2011.10.082
State	Published - Jan 1 2012

Bibliographical note

Funding Information:
This work was supported by a grant from the University of Minnesota AHC .

Keywords

Hint1
Histidine triad binding protein
Inhibitor
Phosphoramidase

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AU - Ghosh, Brahma

AU - Wagner, Carston R.

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KW - Inhibitor

KW - Phosphoramidase

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

Abstract

Bibliographical note

Keywords

UN SDGs

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