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161.
162.
Gharib M Marcantonio M Lehmann SG Courcelles M Meloche S Verreault A Thibault P 《Molecular & cellular proteomics : MCP》2009,8(3):506-518
Sulfation and phosphorylation are post-translational modifications imparting an isobaric 80-Da addition on the side chain of serine, threonine, or tyrosine residues. These two post-translational modifications are often difficult to distinguish because of their similar MS fragmentation patterns. Targeted MS identification of these modifications in specific proteins commonly relies on their prior separation using gel electrophoresis and silver staining. In the present investigation, we report a potential pitfall in the interpretation of these modifications from silver-stained gels due to artifactual sulfation of serine, threonine, and tyrosine residues by sodium thiosulfate, a commonly used reagent that catalyzes the formation of metallic silver deposits onto proteins. Detailed MS analyses of gel-separated protein standards and Escherichia coli cell extracts indicated that several serine, threonine, and tyrosine residues were sulfated using silver staining protocols but not following Coomassie Blue staining. Sodium thiosulfate was identified as the reagent leading to this unexpected side reaction, and the degree of sulfation was correlated with increasing concentrations of thiosulfate up to 0.02%, which is typically used for silver staining. The significance of this artifact is discussed in the broader context of sulfation and phosphorylation site identification from in vivo and in vitro experiments. 相似文献
163.
164.
Zhao Z O'Brien JA Lemaire W Williams DL Jacobson MA Sur C Pettibone DJ Tiller PR Smith S Hartman GD Wolkenberg SE Lindsley CW 《Bioorganic & medicinal chemistry letters》2006,16(23):5968-5972
This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of potent and selective non-sarcosine-derived GlyT1 inhibitors. 相似文献
165.
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Renock S Xu K Pokross M Zhou S Winter C Walter R Mekel M Evdokimov AG 《Bioorganic & medicinal chemistry letters》2006,16(21):5517-5522
A new series of potent 8-hydroxyquinolines was designed based on the newly resolved X-ray crystal structure of EGLN-1. Both alkyl and aryl 8-hydroxyquinoline-7-carboxyamides were good HIF-1alpha prolyl hydroxylase (EGLN) inhibitors. In subsequent VEGF induction assays, these exhibited potent VEGF activity. In addition, this class of compounds did show the ability to stabilize HIF-1alpha. 相似文献
166.
Sabat M VanRens JC Laufersweiler MJ Brugel TA Maier J Golebiowski A De B Easwaran V Hsieh LC Walter RL Mekel MJ Evdokimov A Janusz MJ 《Bioorganic & medicinal chemistry letters》2006,16(23):5973-5977
This communication details the synthesis, biological activity, and binding mode of a novel class of 2-benzimidazole substituted pyrimidines. The most potent analogs disclosed showed low nanomolar activity for the inhibition of Lck kinase and a representative analog was co-crystallized with Hck (a structurally related member of the Src family kinases). 相似文献
167.
Finley DR Bell MG Borel AG Bloomquist WE Cohen ML Heiman ML Kriauciunas A Matthews DP Miles T Neel DA Rito CJ Sall DJ Shuker AJ Stephens TW Tinsley FC Winter MA Jesudason CD 《Bioorganic & medicinal chemistry letters》2006,16(21):5691-5694
The synthesis and biological evaluation of a series of benzimidazolone beta(3) adrenergic receptor agonists are described. A trend toward the reduction of rat atrial tachycardia upon increasing steric bulk at the 3-position of the benzimidazolone moiety was observed. 相似文献
168.
Louise Solveig Nørgaard Dorthe Marlene Götz Mikkelsen Morten Elmeros Mariann Chriél Aksel Bo Madsen Jeppe Lund Nielsen Cino Pertoldi Ettore Randi Joerns Fickel Slaska Brygida Aritz Ruiz-González 《Biological invasions》2017,19(5):1637-1652
The raccoon dog (Nyctereutes procyonoides) has a wide distribution in Europe and is a prominent example of a highly adaptable alien species. It has been recorded sporadically in Denmark since 1980 but observations since 2008 suggested that the species had established a free-ranging, self-sustaining population. To elucidate the origin and genetic patterns of Danish raccoon dogs, we studied the population genomics of 190 individuals collected in Denmark (n = 141) together with reference captive individuals from Poland (n = 21) and feral individuals from different European localities (Germany, Poland, Estonia and Finland, n = 28). We used a novel genotyping-by-sequencing approach simultaneously identifying and genotyping a large panel of single nucleotide polymorphisms (n = 4526). Overall, there was significant indication for contemporary genetic structuring of the analysed raccoon dog populations, into at least four different clusters, in spite of the existence of long distance gene flow and secondary admixture from different population sources. The Danish population was characterized by a high level of genetic admixture with neighbouring feral European ancestries and the presence of private clusters, non-retrieved in any other feral or captive populations sampled. These results suggested that the raccoon dog population in Denmark was founded by escapees from genetically unidentified Danish captive stocks, followed by a recent admixture with individuals migrating from neighbouring Germany. 相似文献
169.
170.
Phospholipase A2 (PLA2) lipolytic activity can be regarded as a limiting factor for the development of inflammatory processes by restricting the production of pro-inflammatory mediators, hence representing a valuable therapeutic target for drugs that are able to modulate the activity of this enzyme. In the current work, the hydrolysis of phospholipids by PLA2 was monitored with acrylodan-labelled intestinal fatty acid binding protein (ADIFAB) and this fluorescence based technique was also used to access the enzymatic inhibitory effect of non-steroidal anti-inflammatory drugs (NSAIDs). The intrinsic fluorescence of PLA2 tryptophan residues was further used to gain complementary information regarding the accessibility of these residues on the PLA2 structure upon interaction with the NSAIDs tested; and to calculate the NSAIDs-PLA2 binding constants. Finally, circular dichroism (CD) measurements were performed to evaluate changes in PLA2 conformation resultant from the inhibitory effect of the drugs tested. Overall, results gathered in this study point to the conclusion that the studied NSAIDs inhibit PLA2 activity due to a disturbance of the enzyme binding efficiency to membrane interface possibly by a shielding effect of the Trp residues required for the membrane interfacial binding step that precedes lipolysis process. 相似文献