Evidence for a multivalent effect in inhibition of sulfatases involved in lysosomal storage disorders (LSDs)

Year: 2016

Authors: D’Adamio G., Matassini C., Parmeggiani C., Catarzi S., Morrone A., Goti A., Paoli P., Cardona F.

Autors Affiliation: Univ Florence, Dept Chem Ugo Schiff, Via Lastruccia 3-13, I-50019 Sesto Fiorentino, FI, Italy; CNR, INO, Via N Carrara 1, I-50019 Sesto Fiorentino, FI, Italy; LENS, Via N Carrara 1, I-50019 Sesto Fiorentino, FI, Italy; Univ Florence, Dept Neurosci Pharmacol & Child Hlth, Meyer Childrens Hosp, Paediat Neurol Unit & Labs,Neurosci Dept, Viale Pieraccini 24, I-50139 Florence, Italy; Univ Florence, Dept Expt & Clin Biomed Sci, Viale Morgagni 50, I-50134 Florence, Italy.

Abstract: Two newly synthesized nonavalent polyhydroxylated pyrrolidine iminosugars are the first examples of multivalent inhibitors of GALNS and IDS lysosomal enzymes, whose deficiency leads to Morquio A syndrome and Hunter disease, respectively, and pave the way to a pharmacological chaperone or stabilizing enzyme therapy for these LSDs.

Journal/Review: RSC ADVANCES

Volume: 6 (69)      Pages from: 64847  to: 64851

More Information: This work was supported by the Italian Ministry of Health (grant Ricerca Finalizzata RF-2011-02347694 to AM and FC) and by MIUR-Italy (PRIN 2010-2011, 2010L9SH3K 006 to AG). Ente Cassa di Risparmio di Firenze is acknowledged for a fellowship to CM (grant No 2013/0366) and to GD (grant No 2014/0303). AM and SC also thank AIMPS (Associazione Italiana Mucopolisaccaridosi e malattie affini), AMMeC (Associazione Malattie Metaboliche e Congenite, Italia) and Fondazione Meyer ONLUS, Firenze for their technical support in computer assistance. CP also thanks the European Research Council (ERC Grant agreement 291349).
KeyWords: Enzyme Replacement Therapy; Iminosugar Click Clusters; Pharmacological Chaperones; Gaucher-disease; Hyacinthacine A(2); Diagnosis; Morquio; Glucocerebrosidase; 7-deoxycasuarine; Architectures
DOI: 10.1039/c6ra15806d

Citations: 18
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