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We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.
Pubmed ID: 25004277 RIS Download
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pTARGET is a computational method to predict the subcellular localization of only eukaryotic proteins from animal species that include fungi and metazoans. Predictions are carried out based on the occurrence patterns of protein functional domains and the amino acid compositional differences in proteins from different subcellular locations. This method can predict proteins targeted to nine distinct subcellular locations that include cytoplasm, endoplasmic reticulum, extracellular/secreted, Golgi, lysosomes, mitochondria, nucleus, peroxysomes and plasma membrane. Current predictions are based on Pfam database version 19.0. Datasets used for developing pTarget method are available.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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