title: Synthesis and evaluation of potential inhibitors of human and Escherichia coli histidine triad nucleotide binding proteins.
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.
authors: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Sanaa K
authors: SK
authors: Bardaweel
authors: Brahma
authors: B
authors: Ghosh
authors: Carston R
authors: CR
authors: Wagner
mesh_terms: D002244:Carbon / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004926:Escherichia coli / Q000378:metabolism*; D004952:Esters / Q000737:chemistry; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D010539:Permeability; D010641:Phenotype; D011485:Protein Binding; D012265:Ribonucleotides / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D004952:Esters; D012265:Ribonucleotides; C097552:histidine triad protein; D002244:Carbon; D006867:Hydrolases