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| Chang, Hui-Hwa; Asano, Naoki; Ishii, Satoshi; Ichikawa, Yoshitaka; Fan, Jian-Qiang. |
| Gaucher disease is an autosomal recessive lysosomal storage disorder caused by the deficient activity of glucocerebrosidase. Accumulation of glucosylceramide, primarily in the lysosomes of cells of the reticuloendothelial system, leads to hepatosplenomegaly, anemia and skeletal lesions in type I disease, and neurologic manifestations in types II and III disease. We report herein the identification of hydrophilic active-site-specific chaperones that are capable of increasing glucocerebrosidase activity in the cultured fibroblasts of Gaucher patients. Screening of a variety of natural and synthetic alkaloid compounds showed isofagomine, N-dodecyl deoxynojirimycin, calystegines A(3), B-1, B-2 and C-1, and 1,5-dideoxy-1,5-iminoxylitol to be potent inhibitors... |
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Palavras-chave: Active-site-specific chaperone; Drug design; Gaucher disease; Glucocerebrosidase; Isofagomine. |
| Ano: 2006 |
URL: http://ir.obihiro.ac.jp/dspace/handle/10322/814 |
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| Shin, In-Sun; Nishikawa, Kiyotaka; Maruyama, Hiroki; Ishii, Satoshi. |
| A two-step binding assay for globotriaosylceramide (Gb3) content was developed by histidine-tagging strategy, which is a well-established method for the purification of recombinant proteins. The complete binding of the recombinant His-tagged Shiga toxin 1B subunit (1B-His) (1 microg/ml) to the standard Gb3 adsorbed on a multi-well H type plate was observed within 30 min at 37 degrees C; and its binding could be visualized by the following applications of HisProbe-HRP (8 microg/ml) and tetramethylbenzidine (TMB) peroxidase substrate. The 1B-His binding assay was linear over the range of 1 to 100 ng of Gb3 per well. The binding of 1B-His was specific to Gb3 separated from HeLa cells, and no major cross-reactivity of other glycolipids in Folch's lower... |
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Palavras-chave: Globotriaosylceramide; Shiga toxin; Binding assay method; His-tagged protein. |
| Ano: 2006 |
URL: http://ir.obihiro.ac.jp/dspace/handle/10322/833 |
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