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Multimerization of DAB-1 onto Au GNPs affords new potent and selective N-acetylgalactosamine-6-sulfatase (GALNS) inhibitors

  Articoli su Riviste JCR/ISI  (anno 2018)

Autori:  Matassini C., Vanni C., Goti A., Morrone A., Marradi M., Cardona F

Affiliazione Autori:  Univ Firenze, Dept Chem Ugo Schiff, Via Lastruccia 3-13, Sesto Fiorentino, FI, Italy; CNR, INO, Via N Carrara 1, Sesto Fiorentino, FI, Italy; LENS, Via N Carrara 1, Sesto Fiorentino, FI, Italy; Univ Bari, Consorzio Interuniv Nazl Ric Metodol & Proc Innov, I-70125 Bari, Italy; Univ Florence, Meyer Childrens Hosp, Neurosci Dept, Paediat Neurol Unit & Labs, Viale Pieraccini 24, I-50139 Florence, Italy; Univ Florence, Dept Neurosci Pharmacol & Child Hlth, Viale Pieraccini 24, I-50139 Florence, Italy; CIC BiomaGUNE, P Miramon 182, Donostia San Sebastian, Spain; CIBER BBN, P Miramon 182, Donostia San Sebastian, Spain; CIDETEC, Biomat Unit, P Miramon 196, Donostia San Sebastian, Spain

Riassunto:  Gold glyconanoparticles (Au GNPs) decorated with the natural iminosugar DAB-1 at different densities are reported. These new multivalent iminosugar architectures strongly and selectively inhibit N-acetylgalactosamine-6-sulfatase (GALNS), whose deficiency is connected to the lysosomal storage disease Morquio A. The combination of the dendrimeric technique with the synthetic strategy employed for Au GNP preparation allowed the enhancement of the multivalent presentation of the iminosugar onto the surface of gold nanoparticles, which resulted in the best GALNS inhibitor reported to date (IC50 = 520 nM).

Rivista/Giornale:  ORGANIC & BIOMOLECULAR CHEMISTRY
Volume n.:  16 (44)      Pagine da: 8604  a: 8612
DOI: 10.1039/c8ob02587h


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