Words similar to appppa
Example sentences for: appppa
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If the substrate-dependent signaling model is correct, then compound 6b, as a nearly isosteric AppppA analog with a low K i , may promote Fhit signaling in Fhit+ cells.
Human Fhit [ 14 ] and the S. cerevisiae Fhit homolog [ 13 ] , which was called Aph1 but is here termed Hnt2 under nomenclature aproved by the Saccharomyces Genome Database, cleave ApppA more readily while Aph1, the S. pombe homolog, cleaves AppppA more readily [ 20 ] . Consistent with the ApppA hydrolase activity of purified Fhit protein, most cancer cell lines that are Fhit negative at the protein level have higher levels of ApppA than cell lines that are Fhit positive [ 21 ] . Nonetheless, the actual concentrations of dinucleoside polyphosphates were submicromolar in every cell culture sample [ 21 ] and thus, under the reported culture conditions, the measured dinucleoside polyphosphates would not be expected to occupy the Fhit active site substantially [ 19 ] . Dinucleoside polyphosphate levels were measured in adenine-requiring S. cerevisiae strains before or after disruption of the Fhit-homologous HNT2 gene [ 13 ] and in adenine-requiring S. pombe strains as a function of disruption and overexpression of the Fhit-homologous aph1 gene [ 22 ] . Recently, it was observed that diadenosine polyphosphates undergo a divalent cation-dependent conformational change that might mediate their biosynthesis, catabolism or signaling properties [ 23 ] .
However, deletion of lysU had no effect on heat-shock inducible AppppA accumulation [ 37 ] . The KRS1 gene [ 38 ] encoding cytosolic lysyl tRNA synthetase was cloned into multicopy plasmid pRS423 [ 39 ] to generate plasmid pM1.
Earlier, Blackburn and co-workers made "supercharged" methane-trisphosphonic acid AppppA analogs containing a central carbon from which three adenylate or phosphate moieties are bonded [ 15 ] . In work presented here, tripodal inhibitors 15a and 17a showed, respectively, micromolar and submicromolar efficacies while the phosphorothioate counterparts 15b and 17b showed 100 nM efficacy.
Phosphorothioate analogs 6b and 12b that preserve the α-β bridging oxygen but substitute carbon for the β phosphorus, achieving 65 to 75-fold binding advantages over AppppA, are expected to be critical for cell biological characterization.
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