Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable multivalent effects towards jack bean a-mannosidase and a Golgi a-mannosidase from Drosophila melanogaster, as well as a good selectivity with respect to a lysosomal a-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 a-mannosidase. TEM studies suggested a binding mode that involves the formation of aggregates, which result from the intermolecular crosslinked network of interactions between the multivalent inhibitors and two or more dimers of JBMan heterodimeric subunits.

Mechanistic Insight into the Binding of Multivalent Pyrrolidines to a-Mannosidases / Mirabella, Stefania; D'Adamio, Giampiero; Matassini, Camilla; Goti, Andrea; Delgado, Sandra; Gimeno, Ana; Robina, Inmaculada; Moreno Vargas, Antonio J.; Šesták, Sergej; JIMENEZ BARBERO, Jesus; Cardona, Francesca. - In: CHEMISTRY. - ISSN 1521-3765. - STAMPA. - 23:(2017), pp. 14585-14596. [10.1002/chem.201703011]

Mechanistic Insight into the Binding of Multivalent Pyrrolidines to a-Mannosidases

MIRABELLA, STEFANIA
Membro del Collaboration Group
;
D'ADAMIO, GIAMPIERO
Membro del Collaboration Group
;
MATASSINI, CAMILLA
Membro del Collaboration Group
;
GOTI, ANDREA
Membro del Collaboration Group
;
JIMENEZ BARBERO, JESUS
Membro del Collaboration Group
;
CARDONA, FRANCESCA
Membro del Collaboration Group
2017

Abstract

Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable multivalent effects towards jack bean a-mannosidase and a Golgi a-mannosidase from Drosophila melanogaster, as well as a good selectivity with respect to a lysosomal a-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 a-mannosidase. TEM studies suggested a binding mode that involves the formation of aggregates, which result from the intermolecular crosslinked network of interactions between the multivalent inhibitors and two or more dimers of JBMan heterodimeric subunits.
2017
23
14585
14596
Mirabella, Stefania; D'Adamio, Giampiero; Matassini, Camilla; Goti, Andrea; Delgado, Sandra; Gimeno, Ana; Robina, Inmaculada; Moreno Vargas, Antonio J.; Šesták, Sergej; JIMENEZ BARBERO, Jesus; Cardona, Francesca
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1100003
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