title: Development of sigma-1 (σ1) receptor fluorescent ligands as versatile tools to study σ1 receptors.
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.
authors.affiliation: Dipartimento di Farmacia-Scienze Del Farmaco, Università Degli Studi di Bari ALDO MORO, Via Orabona 4, I-70125, Bari, Italy. Electronic address: carmen.abate@uniba.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Abate
authors.affiliation: Department of Oncology, University of Turin, Via Santena 5/bis, 10126, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Riganti
authors.affiliation: Dipartimento di Farmacia-Scienze Del Farmaco, Università Degli Studi di Bari ALDO MORO, Via Orabona 4, I-70125, Bari, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Pati
authors.affiliation: Department of Oncology, University of Turin, Via Santena 5/bis, 10126, Torino, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ghigo
authors.affiliation: Dipartimento di Farmacia-Scienze Del Farmaco, Università Degli Studi di Bari ALDO MORO, Via Orabona 4, I-70125, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardi
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
authors.forename: Timur
authors.initials: T
authors.lastname: Mavlyutov
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
authors.forename: Lian-Wang
authors.initials: LW
authors.lastname: Guo
authors.affiliation: Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ruoho
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D005434:Flow Cytometry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D015394:Molecular Structure; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: Fluorescent ligand; Sigma receptors