Despite their controversial physiology, sigma-1 (σ1) receptors are intriguing targets for the development of therapeutic agents for central nervous system diseases. With the aim of providing versatile pharmacological tools to study σ1 receptors, we developed three σ1 fluorescent tracers by functionalizing three well characterized σ1 ligands with a fluorescent tag. A good compromise between σ1 binding affinity and fluorescent properties was reached, and the σ1 specific targeting of the novel tracers was demonstrated by confocal microscopy and flow cytometry. These novel ligands were also successfully used in competition binding studies by flow cytometry, showing their utility in nonradioactive binding assays as an alternative strategy to the more classical radioligand binding assays. To the best of our knowledge these are the first σ1 fluorescent ligands to be developed and successfully employed in living cells, representing promising tools to strengthen σ1 receptors related studies.

Development of sigma-1 (σ1) receptor fluorescent ligands as versatile tools to study σ1 receptors

RIGANTI, Chiara;GHIGO, Dario Antonio;
2016-01-01

Abstract

Despite their controversial physiology, sigma-1 (σ1) receptors are intriguing targets for the development of therapeutic agents for central nervous system diseases. With the aim of providing versatile pharmacological tools to study σ1 receptors, we developed three σ1 fluorescent tracers by functionalizing three well characterized σ1 ligands with a fluorescent tag. A good compromise between σ1 binding affinity and fluorescent properties was reached, and the σ1 specific targeting of the novel tracers was demonstrated by confocal microscopy and flow cytometry. These novel ligands were also successfully used in competition binding studies by flow cytometry, showing their utility in nonradioactive binding assays as an alternative strategy to the more classical radioligand binding assays. To the best of our knowledge these are the first σ1 fluorescent ligands to be developed and successfully employed in living cells, representing promising tools to strengthen σ1 receptors related studies.
2016
108
577
585
http://www.journals.elsevier.com/european-journal-of-medicinal-chemistry/
Fluorescent ligand; Sigma receptors; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; Pharmacology
Abate, Carmen; Riganti, Chiara; Pati, Maria Laura; Ghigo, Dario; Berardi, Francesco; Mavlyutov, Timur; Guo, Lian-Wang; Ruoho, Arnold
File in questo prodotto:
File Dimensione Formato  
Post-print Abate Eur J Med Chem MS and Supporting 2016.pdf

Accesso aperto

Descrizione: versione open access post-print Abate, Eur J Med Chem, 2016
Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 1.84 MB
Formato Adobe PDF
1.84 MB Adobe PDF Visualizza/Apri
Abate Eur J Med Chem MS and Suppl 2016.pdf

Accesso riservato

Descrizione: PDF editorale, accesso riservato, Abate, Eur J Med Chem, 2016
Tipo di file: PDF EDITORIALE
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1556537
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 11
social impact