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Recently, we found that bicyclic nojirimycin (NJ) derivatives of the sp<jats:sup>2<\/jats:sup>\u2010iminosugar type, including the 6\u2010thio\u2010<jats:italic>N\u2032<\/jats:italic>\u2010octyl\u2010(5<jats:italic>N<\/jats:italic>,6<jats:italic>S<\/jats:italic>)\u2010octyliminomethylidene derivative (6S\u2010NOI\u2010NJ), behaved as very selective competitive inhibitors of the lysosomal \u03b2\u2010Glu and exhibited remarkable chaperone activities for several GD mutations. To obtain information about the cellular uptake pathway and intracellular distribution of this family of chaperones, we have synthesized a fluorescent analogue that maintains the fused piperidine\u2013thiazolidine bicyclic skeleton and incorporates a dansyl group in the <jats:italic>N\u2032<\/jats:italic>\u2010substituent, namely 6\u2010thio\u2010(5<jats:italic>N<\/jats:italic>,6<jats:italic>S<\/jats:italic>)\u2010[4\u2010(<jats:italic>N\u2032<\/jats:italic>\u2010dansylamino)butyliminomethylidene]nojirimycin (6S\u2010NDI\u2010NJ). This structural modification does not significantly modify the biological activity of the glycomimetic as a chemical chaperone. Our study showed that 6S\u2010NDI\u2010NJ is mainly located in lysosome\u2010related organelles in both normal and GD fibroblasts, and the fluorescent intensity of 6S\u2010NDI\u2010NJ in the lysosome is related to the \u03b2\u2010Glu concentration level. 6S\u2010NDI\u2010NJ also can enter cultured neuronal cells and act as a chaperone. Competitive inhibition studies of 6S\u2010NDI\u2010NJ uptake in fibroblasts showed that high concentrations of <jats:sc>D<\/jats:sc>\u2010glucose have no effect on chaperone internalization, suggesting that it enters the cells through glucose\u2010transporter\u2010independent mechanisms.<\/jats:p>","DOI":"10.1002\/cbic.201000323","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T12:17:31Z","timestamp":1289305051000},"page":"2453-2464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A Fluorescent sp<sup>2<\/sup>\u2010Iminosugar With Pharmacological Chaperone Activity for Gaucher Disease: Synthesis and Intracellular Distribution Studies"],"prefix":"10.1002","volume":"11","author":[{"given":"Zhuo","family":"Luan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Higaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Aguilar\u2010Moncayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruaki","family":"Ninomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Nanba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousaku","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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