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Deficits resulting from missense mutations may become treatable by small, competitive inhibitors binding to the catalytical site and thus correcting the erroneous conformation of mutant enzymes. This may prevent their premature degradation and normalize intracellular trafficking as well as biological half\u2010life. A major limitation currently arises from the huge number of individual missense mutations and the lack of knowledge on the structural requirements for specific interaction with mutant protein domains. Our previous work on mutations of the \u03b2\u2010galactosidase (\u03b2\u2010gal) gene, causing GM1 gangliosidosis (GM1) and Morquio B disease (MBD), respectively, characterized clinical phenotypes as well as biosynthesis, intracellular transport and subcellular localization of mutants. We recently identified an effective chaperone, DL\u2010HexDGJ (Methyl 6\u2010{[N<jats:sup>2<\/jats:sup>\u2010(dansyl)\u2010N<jats:sup>6<\/jats:sup>\u2010(1,5\u2010dideoxy\u2010D\u2010galactitol\u20101,5\u2010diyl)\u2010 L\u2010lysyl]amino} hexanoate), among a series of N\u2010modified 1\u2010deoxygalactonojirimycin derivatives carrying a dansyl group in its N\u2010acyl moiety. Using novel and flexible synthetic routes, we now report on the effects of two oligofluoroalkyl\u2010derivatives of 1\u2010deoxygalactonojirimycin, Ph(TFM)<jats:sub>2<\/jats:sub>OHex\u2010DGJ (N\u2010(\u03b1,\u03b1\u2010di\u2010trifluoromethyl) benzyloxyhexyl\u20101,5\u2010dideoxy\u20101,5\u2010imino\u2010<jats:sc>d<\/jats:sc>\u2010galactitol) and (TFM)<jats:sub>3<\/jats:sub>OHex\u2010DGJ (<jats:italic>N<\/jats:italic>\u2010(Nonafluoro\u2010<jats:italic>tert<\/jats:italic>\u2010butyloxy)hexyl\u20101,5\u2010dideoxy\u20101,5\u2010imino\u2010<jats:sc>d<\/jats:sc>\u2010galactitol) on the \u03b2\u2010gal activity of GM1 and MBD fibroblasts. Both compounds are competitive inhibitors and increase the residual enzyme activities up to tenfold over base line activity in GM1 fibroblasts with chaperone\u2010sensitive mutations. Western blots showed that this was due to a normalization of protein transport and intralysosomal maturation. The fact that the novel compounds were effective at very low concentrations (0.5\u201310 \u03bcM) in the cell culture medium as well as their novel chemical character suggest future testing in animal models. This may contribute to new aspects for efficient and personalized small molecule treatment of lysosomal storage diseases.<\/jats:p>","DOI":"10.1007\/s10545-011-9409-2","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T19:34:55Z","timestamp":1319744095000},"page":"495-503","source":"Crossref","is-referenced-by-count":22,"title":["Fluorous iminoalditols act as effective pharmacological chaperones against gene products from <i>GLB1<\/i> alleles causing G<sub>M1<\/sub>\u2010gangliosidosis and Morquio B disease"],"prefix":"10.1002","volume":"35","author":[{"given":"Katrin M.","family":"Fantur","sequence":"first","affiliation":[{"name":"Department of Pediatrics Medical University of Graz Graz Austria"},{"name":"The Wenner\u2010Gren Institute for Experimental Biology Stockholm University Svante Arrheniusv\u00e4g 20B Stockholm S\u201010691 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja M.","family":"Wrodnigg","sequence":"additional","affiliation":[{"name":"Glycogroup, Department of Organic Chemistry Graz University of Technology Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold E.","family":"St\u00fctz","sequence":"additional","affiliation":[{"name":"Glycogroup, Department of Organic Chemistry Graz University of Technology Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina M.","family":"Pabst","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Paschke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical University of Graz Graz Austria"},{"name":"Laboratory of Metabolic Diseases, Department of Pediatrics Medical University of Graz Auenbruggerplatz 34 Graz A\u20108036 Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320010205"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwg090"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(02)00172-2"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784705504"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1077-0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.04.012"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2008.03.004"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(99)00075-7"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2008.009"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.03.019"},{"key":"e_1_2_5_12_1","first-page":"23","article-title":"Morquio syndrome (mucopolysaccharidosis IVB) associated with \u03b2\u2010galactosidase deficiency. 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