The synthesis of multivalent ligands able to selectively bind enzymes has produced a multitude of new glycomimetics anchored to different macrocyclic scaffolds. However, in this scenario, the studies focused on therapeutically relevant enzymes are still scarce. Resorcinarenes offer the opportunity to attach several bioactive functions to different positions, thereby accessing different topologies of the multivalent constructs. In this work, multimerization of the pyrrolidine iminosugar DAB-1 onto resorcinarene scaffolds has been addressed. The synthesized new architectures show a remarkable multivalent effect towards GMIIb, the recombinant Drosophila homolog of the tumor over-expressed human Golgi α-mannosidase II, over other α-mannosidases. Computational studies shed light on the origin of their multivalent effect as well as on their relative inhibitory potency.

Multivalent resorcinarene clusters decorated with DAB-1 inhitopes: targeting Golgi α-mannosidase from Drosophila melanogaster / Paolo Della Sala, Costanza Vanni, Carmen Talotta, Luca Di Marino, Camilla Matassini, Andrea Goti, Placido Neri, Sergej Šesták, Francesca Cardona, Carmine Gaeta. - In: ORGANIC CHEMISTRY FRONTIERS. - ISSN 2052-4110. - STAMPA. - 2021:(2021), pp. 6648-6656. [10.1039/d1qo01048d]

Multivalent resorcinarene clusters decorated with DAB-1 inhitopes: targeting Golgi α-mannosidase from Drosophila melanogaster

Costanza Vanni
Membro del Collaboration Group
;
Camilla Matassini
Membro del Collaboration Group
;
Andrea Goti
Membro del Collaboration Group
;
Francesca Cardona
Conceptualization
;
2021

Abstract

The synthesis of multivalent ligands able to selectively bind enzymes has produced a multitude of new glycomimetics anchored to different macrocyclic scaffolds. However, in this scenario, the studies focused on therapeutically relevant enzymes are still scarce. Resorcinarenes offer the opportunity to attach several bioactive functions to different positions, thereby accessing different topologies of the multivalent constructs. In this work, multimerization of the pyrrolidine iminosugar DAB-1 onto resorcinarene scaffolds has been addressed. The synthesized new architectures show a remarkable multivalent effect towards GMIIb, the recombinant Drosophila homolog of the tumor over-expressed human Golgi α-mannosidase II, over other α-mannosidases. Computational studies shed light on the origin of their multivalent effect as well as on their relative inhibitory potency.
2021
2021
6648
6656
Paolo Della Sala, Costanza Vanni, Carmen Talotta, Luca Di Marino, Camilla Matassini, Andrea Goti, Placido Neri, Sergej Šesták, Francesca Cardona,...espandi
File in questo prodotto:
File Dimensione Formato  
OrgChemFront_2021,8,6648-6656.pdf

Accesso chiuso

Descrizione: OrgChemFront 2021,8,6648-6656
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 1.27 MB
Formato Adobe PDF
1.27 MB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1249343
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact