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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Chlorocebus aethiops
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Cocaine / pharmacology
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Dopamine Plasma Membrane Transport Proteins / metabolism*
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Fluorescent Dyes / chemical synthesis*
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Fluorescent Dyes / chemistry
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Humans
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Microscopy, Confocal
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Norepinephrine Plasma Membrane Transport Proteins / metabolism
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Rhodamines / chemistry*
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
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Tropanes / chemical synthesis*
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Tropanes / chemistry
Substances
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Dopamine Plasma Membrane Transport Proteins
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Fluorescent Dyes
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Norepinephrine Plasma Membrane Transport Proteins
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Rhodamines
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Serotonin Plasma Membrane Transport Proteins
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Tropanes
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Cocaine