Article
Mechanistic Insight into the Binding of Multivalent Pyrrolidines to α-Mannosidases
Author/s | Mirabella, Stefania
D'Adamio, Giampiero Matassini, Camilla Goti, Andrea Delgado, Sandra Gimeno, Ana Robina Ramírez, Inmaculada Moreno Vargas, Antonio José Šesták, Sergej Jiménez Barbero, Jesús Cardona, Francesca |
Department | Universidad de Sevilla. Departamento de Química orgánica |
Publication Date | 2017 |
Deposit Date | 2022-12-19 |
Published in |
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Abstract | Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable multivalent effects towards jack bean α-mannosidase and a Golgi α-mannosidase from Drosophila melanogaster, as well ... Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable multivalent effects towards jack bean α-mannosidase and a Golgi α-mannosidase from Drosophila melanogaster, as well as a good selectivity with respect to a lysosomal α-mannosidase, which is important for anticancer applications. STD NMR and molecular modeling studies supported a multivalent mechanism with specific interactions of the bioactive iminosugars with Jack bean α-mannosidase. TEM studies suggested a binding mode that involves the formation of aggregates, which result from the intermolecular cross-linked network of interactions between the multivalent inhibitors and two or more dimers of JBMan heterodimeric subunits. |
Funding agencies | Italian Ministry of Health. Regione Toscana Ministry of Education, Universities and Research (MIUR). Italia Fondazione Cassa Risparmio Firenze Ministerio de Economía y Competitividad (MINECO). España |
Project ID. | RF-2011-02347694
2010L9SH3K 006 2014/0303 CTQ2015-64597-C2-1-P CTQ2012-31247 CTQ2016-77270-R |
Citation | Mirabella, S., D'Adamio, G., Matassini, C., Goti, A., Delgado, S., Gimeno, A.,...,Cardona, F. (2017). Mechanistic Insight into the Binding of Multivalent Pyrrolidines to α-Mannosidases. Chemistry - A European Journal, 23 (58), 14585-14596. https://doi.org/10.1002/chem.201703011. |
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