title: Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter.
abstract: Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane, using an ethylamino linker. The resulting 2-substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the highest DAT binding affinities expressed in COS-7 cells (Ki= 27 and 18 nM, respectively) in the series. Visualization of the DAT with 5 and 9 was demonstrated by confocal fluorescence laser scanning microscopy in stably transfected HEK293 cells.
authors.affiliation: Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Cha
authors.forename: Mu-Fa
authors.initials: MF
authors.lastname: Zou
authors.forename: Erika M
authors.initials: EM
authors.lastname: Adkins
authors.forename: Søren G F
authors.initials: SG
authors.lastname: Rasmussen
authors.forename: Claus Juul
authors.initials: CJ
authors.lastname: Loland
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schoenenberger
authors.forename: Ulrik
authors.initials: U
authors.lastname: Gether
authors.forename: Amy Hauck
authors.initials: AH
authors.lastname: Newman
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003042:Cocaine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005456:Fluorescent Dyes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012235:Rhodamines; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes; D003042:Cocaine