Among carbohydrate-processing enzymes, Jack bean alpha-mannosidase (JB-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 (-D-gluco or-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 JB alpha-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.

Hybrid Multivalent Jack Bean alpha-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. - In: MOLECULES. - ISSN 1420-3049. - STAMPA. - 26:(2021), pp. 5864-5876. [10.3390/molecules26195864]

Hybrid Multivalent Jack Bean alpha-Mannosidase Inhibitors: The First Example of Gold Nanoparticles Decorated with Deoxynojirimycin Inhitopes

Costanza Vanni
Methodology
;
Marco Marradi
Writing – Review & Editing
;
Sergio Moya
Membro del Collaboration Group
;
Andrea Goti
Supervision
;
Francesca Cardona
Funding Acquisition
;
Philippe Compain
Membro del Collaboration Group
;
Camilla Matassini
Conceptualization
2021

Abstract

Among carbohydrate-processing enzymes, Jack bean alpha-mannosidase (JB-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 (-D-gluco or-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 JB alpha-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.
26
5864
5876
Costanza Vanni, Anne Bodlenner , Marco Marradi, Jérémy P. Schneider, Maria de los Angeles Ramirez ,Sergio Moya , Andrea Goti , Francesca Cardona , Philippe Compain,Camilla Matassini
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1245083
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