title: Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease.
abstract: Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells.
authors.affiliation: Laboratoire de Synthèse Organique et Molécules Bioactives (SYBIO), Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France; Research Unit on BioActive Molecules (RUBAM), Departament de Química Biomèdica, Institut de Química Avançada de Catalunya (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Laigre
authors.affiliation: Laboratoire de Synthèse Organique et Molécules Bioactives (SYBIO), Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Hazelard
authors.affiliation: Research Unit on BioActive Molecules (RUBAM), Departament de Química Biomèdica, Institut de Química Avançada de Catalunya (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.affiliation: Departament de Genètica, Universitat de Barcelona (UB), IBUB, CIBER de Enfermedades Raras (CIBERER), Av. Diagonal 645, E-08028, Barcelona, Spain.
authors.forename: Jenny
authors.initials: J
authors.lastname: Serra-Vinardell
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens 11527, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens 11527, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Mavridou
authors.affiliation: Department of Medicinal Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.affiliation: Research Unit on BioActive Molecules (RUBAM), Departament de Química Biomèdica, Institut de Química Avançada de Catalunya (IQAC-CSIC), Jordi Girona 18, 08034 Barcelona, Spain; Unit of Pharmaceutical Chemistry (Associated Unit to CSIC), Department of Pharmacology and Medicinal Chemistry, Faculty of Pharmacy, University of Barcelona (UB), Avga. Joan XXIII s/n, E-08028 Barcelona, Spain. Electronic address: delgado@rubam.net.
authors.forename: Antonio
authors.initials: A
authors.lastname: Delgado
authors.affiliation: Laboratoire de Synthèse Organique et Molécules Bioactives (SYBIO), Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France. Electronic address: philippe.compain@unistra.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Compain
mesh_terms: D057930:Click Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D004793:Enzyme Reactivators / Q000138:chemical synthesis* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005776:Gaucher Disease / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D005962:Glucosylceramidase / Q000737:chemistry* / Q000172:deficiency; D006801:Humans; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009025:Morpholines / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D004793:Enzyme Reactivators; D050111:Imino Sugars; D009025:Morpholines; D011355:Prodrugs; D005962:Glucosylceramidase
keywords: Click-chemistry; Gaucher disease; Iminosugars; Lysosomal diseases; Multivalency; Pharmacological chaperones