Rhodamine-Labeled 2beta-Carbomethoxy-3beta-(3,4-dichlorophenyl)-tropane Analogues as High-Affinity Fluorescent Probes for the Dopamine Transporter

摘要

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-car-bomethoxy-3beta-(3,4-dichlorophenyl)tropane,using an ethylami-no linker.The resulting 2-substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the highest DAT binding affinities expressed in COS-7 cells (K_i=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.