https://scholars.lib.ntu.edu.tw/handle/123456789/525850
Title: | Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency | Authors: | Cheng W.-C. Wang J.-H. Li H.-Y. Lu S.-J. Hu J.-M. Yun W.-Y. Chiu C.-H. Yang W.-B. YIN-HSIU CHIEN WUH-LIANG HWU |
Issue Date: | 2016 | Publisher: | Elsevier Masson SAS | Journal Volume: | 123 | Start page/Pages: | 14-20 | Source: | European Journal of Medicinal Chemistry | Abstract: | A unique molecular library consisting of all sixteen synthetic ADMDP (1-aminodeoxy-DMDP) stereoisomers has been prepared and evaluated for inhibitory activity against α-Gal A, and ability to impart thermal stabilization of this enzyme. The results of this testing led us to develop a novel pharmacological chaperone for the treatment of Fabry disease. 3-Epimer ADMDP was found to be an effective pharmacological chaperone, able to rescue α-Gal A activity in the lymphoblast of the N215S Fabry patient-derived cell line, without impairment of cellular β-galactosidase activity. When 3-epimer ADMDP was administered with rh-α-Gal A (enzyme replacement therapy) for the treatment of Fabry patient-derived cell lines, improvements in the efficacy of rh-α-Gal A was observed, which suggests this small molecule can also provide clinical benefit of enzyme replacement therapy in Fabry disease. ? 2016 |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979643798&doi=10.1016%2fj.ejmech.2016.07.025&partnerID=40&md5=52876c24f6ccad10c80a92e4f6a68cc8 https://scholars.lib.ntu.edu.tw/handle/123456789/525850 |
ISSN: | 0223-5234 | DOI: | 10.1016/j.ejmech.2016.07.025 | SDG/Keyword: | alpha galactosidase; beta galactosidase; glycosidase inhibitor; recombinant human alpha galactosidase; unclassified drug; 1-aminodeoxy-2,5-dideoxy-2,5-iminomannitol; alpha galactosidase; enzyme inhibitor; iminosugar; mannitol; molecular library; pyrrolidine derivative; Article; carbon nuclear magnetic resonance; dose response; drug potency; drug potentiation; drug screening; drug synthesis; enzyme activity; enzyme inhibition; enzyme replacement; epimer; Fabry disease; human; human cell; IC50; isomer; lymphoblast; lysosome; nucleophilicity; pH; proton nuclear magnetic resonance; stereoisomerism; analogs and derivatives; chemistry; drug effects; enzyme replacement; enzyme stability; Fabry disease; molecular library; pharmacology; procedures; stereoisomerism; synthesis; tumor cell line; alpha-Galactosidase; Cell Line, Tumor; Enzyme Inhibitors; Enzyme Replacement Therapy; Enzyme Stability; Fabry Disease; Humans; Imino Pyranoses; Imino Sugars; Mannitol; Pyrrolidines; Small Molecule Libraries; Stereoisomerism |
Appears in Collections: | 醫學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.