{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:42:37Z","timestamp":1787168557263,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["B96C1700020008"],"award-info":[{"award-number":["B96C1700020008"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009888","name":"Regione Toscana","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2024,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Engineering bioactive iminosugars with pH\u2010responsive groups is an emerging approach to develop pharmacological chaperones (PCs) able to improve lysosomal trafficking and enzymatic activity rescue of mutated enzymes. The use of inexpensive\n                    <jats:sc>l<\/jats:sc>\n                    \u2010malic acid allowed introduction of orthoester units into the lipophilic chain of an enantiomerically pure iminosugar affording only two diastereoisomers contrary to previous related studies. The iminosugar was prepared stereoselectively from the chiral pool (\n                    <jats:sc>d<\/jats:sc>\n                    \u2010mannose) and chosen as the lead bioactive compound, to develop novel candidates for restoring the lysosomal enzyme glucocerebrosidase (GCase) activity. The stability of orthoester\u2010appended iminosugars was studied by\n                    <jats:sup>1<\/jats:sup>\n                    H\u2005NMR spectroscopy both in neutral and acidic environments, and the loss of inhibitory activity with time in acid medium was demonstrated on cell lysates. Moreover, the ability to rescue GCase activity in the lysosomes as the result of a chaperoning effect was explored. A remarkable pharmacological chaperone activity was measured in fibroblasts hosting the homozygous L444P\/L444P mutation, a cell line resistant to most PCs, besides the more commonly responding N370S mutation.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202300730","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T07:24:31Z","timestamp":1698218671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["pH\u2010Responsive Trihydroxylated Piperidines Rescue The Glucocerebrosidase Activity in Human Fibroblasts Bearing The Neuronopathic Gaucher\u2010Related L444P\/L444P Mutations in\n                    <i>GBA1<\/i>\n                    Gene"],"prefix":"10.1002","volume":"25","author":[{"given":"Maria Giulia","family":"Davighi","sequence":"first","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"},{"name":"Current address: BioMedical Engineering and Imaging Institute Icahn School of Medicine at Mount Sinai  1470 Madison Ave, New York 10029 New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Matassini","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Paoli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences University of Florence  Viale Morgagni 50 50134 Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Morrone","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Neurometabolic Diseases Meyer Children's Hospital IRCCS  Viale Pieraccini 24 50139 Firenze Italy"},{"name":"Department of Neurosciences Psychology Drug Research and Child Health University of Florence  Viale Pieraccini 24 50139 Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Cacciarini","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"},{"name":"Department of Chemistry University of Copenhagen  Universitetsparken 5 DK-2100 Copenhagen \u00d8 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Goti","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-4624","authenticated-orcid":false,"given":"Francesca","family":"Cardona","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d (DICUS) University of Florence  Via della Lastruccia 3\u201313 50019 Sesto F.no (FI) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901281"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv179"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13517"},{"key":"e_1_2_9_4_1","volume-title":"Advances in Gaucher Disease: Basic and Clinical Perspectives","author":"Grabowski G. 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