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Various Acid (various + acid)
Selected AbstractsChaperone Activity of Bicyclic Nojirimycin Analogues for Gaucher Mutations in Comparison with N -(n -nonyl)DeoxynojirimycinCHEMBIOCHEM, Issue 17 2009Zhuo Luan Abstract Gaucher disease (GD), the most prevalent lysosomal storage disorder, is caused by mutations of lysosomal ,-glucosidase (acid ,-Glu, ,-glucocerebrosidase); these mutations result in protein misfolding. Some inhibitors of this enzyme, such as the iminosugar glucomimetic N -(n -nonyl)-1-deoxynojirimycin (NN-DNJ), are known to bind to the active site and stabilize the proper folding for the catalytic form, acting as "chemical chaperones" that facilitate transport and maturation of acid ,-Glu. Recently, bicyclic nojirimycin (NJ) analogues with structure of sp2 iminosugars were found to behave as very selective, competitive inhibitors of the lysosomal ,-Glu. We have now evaluated the glycosidase inhibitory profile of a series of six compounds within this family, namely 5- N,6- O -(N, -octyliminomethylidene-NJ (NOI-NJ), the 6-thio and 6-amino-6-deoxy derivatives (6S-NOI-NJ and 6N-NOI-NJ) and the corresponding galactonojirimycin (GNJ) counterparts (NOI-GNJ, 6S-NOI-GNJ and 6N-NOI-GNJ), against commercial as well as lysosomal glycosidases. The chaperone effects of four selected candidates (NOI-NJ, 6S-NOI-NJ, 6N-NOI-NJ, and 6S-NOI-GNJ) were further evaluated in GD fibroblasts with various acid ,-Glu mutations. The compounds showed enzyme enhancement on human fibroblasts with N188S, G202R, F213I or N370S mutations. The chaperone effects of the sp2 iminosugar were generally stronger than those observed for NN-DNJ; this suggests that these compounds are promising candidates for clinical treatment of GD patients with a broad range of ,-Glu mutations, especially for neuronopathic forms of Gaucher disease. [source] A Tetranuclear-Zinc-Cluster-Catalyzed Practical and Versatile Deprotection of Acetates and BenzoatesCHEMISTRY - A EUROPEAN JOURNAL, Issue 38 2010Dr. Takanori Iwasaki A new catalytic deacylation of acetates and benzoates through transesterification with methanol was developed (see scheme). Reactions with various acid- and nucleophile-sensitive functional groups proceeded efficiently in the presence of a catalytic amount of the tetranuclear zinc cluster. The present catalysis is applicable to less-reactive tertiary acetates, the deacylation of which is difficult to achieve by transesterification with other catalysts. [source] Rapid throughput screening of apparent KSP values for weakly basic drugs using 96-well formatJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2008Jeremy Guo Abstract A rapid-throughput screening assay was developed to estimate the salt solubility parameter, KSP, with a minimal quantity of drug. This assay allows for early evaluation of salt limited solubility with a large number of counter-ions and biologically promising drug leads. Drugs dissolved (typically 10 mM) in DMSO are robotically distributed to a 96-well plate. DMSO is evaporated, and drugs are equilibrated with various acids at different concentrations (typically <1 M) to yield final total drug concentrations around 2.5 mM. The plate is checked for precipitation. Filtrates from only those precipitated wells were subjected to rapid gradient HPLC analysis. An iterative procedure is employed to calculate all species concentrations based on mass and charge balance equations. The apparent KSP values assuming 1:1 stoichiometry are determined from counter-ion and ionized drug activities. A correlation coefficient >0.975 for eight drugs totaling 16 salts is reported. Intra-day and inter-day reproducibility was <10%. Conventional apparent KSP measurements were translated to 96-well format for increased throughput and minimal drug consumption (typically 10 mg) to evaluate at least eight different counter-ions. Although the current protocol estimates KSP from 10,3 to 10,7 M, the dynamic range of the assay could be expanded by adjusting drug and counter-ion concentrations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2079,2090, 2008 [source] Control of polyaniline conductivity and contact angles by partial protonationPOLYMER INTERNATIONAL, Issue 1 2008Natalia V Blinova Abstract Many studies require a specific value of conductivity when investigating conducting polymers. The conductivity of polyaniline can efficiently be controlled by partial protonation of the polyaniline base. Although this is a simple task in principle, practical guidelines are missing. In the present study, the changes in the conductivity of polyaniline base after immersion in aqueous solutions of various acids are reported. Polyaniline base has been reprotonated in aqueous solutions of picric, camphorsulfonic and phosphoric acids. The conductivity of partially reprotonated polyaniline varied between 10,9 and 100 S cm,1. The relation between the pH of a phosphoric acid solution, which was in equilibrium with polyaniline, and the conductivity , is pH = 0.77 , 0.64 log(, [S cm,1]). The wettability, i.e. water contact angles, can similarly be set by partial protonation to between 78° for polyaniline base and 44° for polyaniline reprotonated in 1 mol L,1 phosphoric acid. In solutions of picric acid, the transition from the non-conducting to the conducting state occurs over a narrow range of acid concentrations, and the tuning of conductivity is consequently difficult. Phosphoric acid is well suited for the control of conductivity of polyaniline because of the moderate dependence of the conductivity on the acid concentration or pH. Copyright © 2007 Society of Chemical Industry [source] | ||||||||||