Hybrid Multivalent Jack Bean α-Mannosidase Inhibitors: The First Example of Gold Nanoparticles Decorated with Deoxynojirimycin Inhitopes
Costanza Vanni,
Anne Bodlenner,
Marco Marradi,
Jérémy P. Schneider,
Maria de los Angeles Ramirez,
Sergio Moya,
Andrea Goti,
Francesca Cardona,
Philippe Compain,
Camilla Matassini
Affiliations
Costanza Vanni
Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Anne Bodlenner
Laboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, France
Marco Marradi
Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Jérémy P. Schneider
Laboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, France
Maria de los Angeles Ramirez
Soft Matter Nanotechnology Lab, CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014 Donostia-San Sebastián, Gipuzkoa, Spain
Sergio Moya
Soft Matter Nanotechnology Lab, CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014 Donostia-San Sebastián, Gipuzkoa, Spain
Andrea Goti
Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Francesca Cardona
Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Philippe Compain
Laboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, France
Camilla Matassini
Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Among carbohydrate-processing enzymes, Jack bean α-mannosidase (JBα-man) is the glycosidase with the best responsiveness to the multivalent presentation of iminosugar inhitopes. We report, in this work, the preparation of water dispersible gold nanoparticles simultaneously coated with the iminosugar deoxynojirimycin (DNJ) inhitope and simple monosaccharides (β-d-gluco- or α-d-mannosides). The display of DNJ at the gold surface has been modulated (i) by using an amphiphilic linker longer than the aliphatic chain used for the monosaccharides and (ii) by presenting the inhitope, not only in monomeric form, but also in a trimeric fashion through combination of a dendron approach with glyconanotechnology. The latter strategy resulted in a strong enhancement of the inhibitory activity towards JBα-man, with a Ki in the nanomolar range (Ki = 84 nM), i.e., more than three orders of magnitude higher than the monovalent reference compound.
