title: Cell uptake and localization studies of squaramide based fluorescent probes.
abstract: Cell internalization is a major issue in drug design. Although squaramide-based compounds are receiving much attention because of their interesting bioactivity, cell uptake and trafficking within cells of this type of compounds are still unknown. In order to monitor the cell internalization process of cyclosquaramide compounds we have prepared two fluorescent probes by covalently linking a fluorescent dye (BODIPY derivative or fluorescein) to a noncytotoxic cyclosquaramide framework. These two probes (C2-BDP and C2-FITC) rapidly internalize across live cell membranes through endocytic receptor-mediated mechanisms. Due to its higher fluorescence and photochemical stability, C2-BDP is a superior dye than C2-FITC. C2-BDP remains sequestered in late endosomes allowing their fast and selective imaging in various live cell types. Cyclosquaramide-cell membrane interactions facilitate cell uptake and have been investigated by binding studies in solution as well as in live cells. Cyclosquaramide 1 (C2-BDP) can be used as a highly fluorescent probe for the rapid and selective imaging of late endosomes in live cells.
authors.affiliation: Departament de Química, ‡Departament de Biologia Fonamental, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS) and Instituto de Investigación Sanitaria de Palma (IdISPa), Illes Balears, Spain, Universitat de les Illes Balears , Ctra. Valldemossa km 7.5, 07122 Palma, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Sampedro
authors.forename: Ruth
authors.initials: R
authors.lastname: Villalonga-Planells
authors.forename: Manuel
authors.initials: M
authors.lastname: Vega
authors.forename: Guillem
authors.initials: G
authors.lastname: Ramis
authors.forename: Silvia
authors.initials: S
authors.lastname: Fernández de Mattos
authors.forename: Priam
authors.initials: P
authors.lastname: Villalonga
authors.forename: Antoni
authors.initials: A
authors.lastname: Costa
authors.forename: Carmen
authors.initials: C
authors.lastname: Rotger
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D001692:Biological Transport; D001896:Boron Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003503:Cyclobutanes / Q000737:chemistry* / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D055668:Photochemical Processes
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000577:Amides; D001896:Boron Compounds; D003503:Cyclobutanes; D005456:Fluorescent Dyes; C030042:squaric acid