Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

Joo Hwan Cha; Mu-Fa Zou; Erika M Adkins; Søren G F Rasmussen; Claus Juul Loland; Bernhard Schoenenberger; Ulrik Gether; Amy Hauck Newman

doi:10.1021/jm050431y

Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

Joo Hwan Cha, Mu-Fa Zou, Erika M Adkins, Søren G F Rasmussen, Claus Juul Loland, Bernhard Schoenenberger, Ulrik Gether, Amy Hauck Newman

33 Citations (Scopus)

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.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	24
Pages (from-to)	7513-6
Number of pages	4
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm050431y
Publication status	Published - 1 Dec 2005

Keywords

Animals
Cell Line
Cercopithecus aethiops
Cocaine
Dopamine Plasma Membrane Transport Proteins
Fluorescent Dyes
Humans
Microscopy, Confocal
Norepinephrine Plasma Membrane Transport Proteins
Rhodamines
Serotonin Plasma Membrane Transport Proteins
Structure-Activity Relationship
Tropanes

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10.1021/jm050431y

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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.",

keywords = "Animals, Cell Line, Cercopithecus aethiops, Cocaine, Dopamine Plasma Membrane Transport Proteins, Fluorescent Dyes, Humans, Microscopy, Confocal, Norepinephrine Plasma Membrane Transport Proteins, Rhodamines, Serotonin Plasma Membrane Transport Proteins, Structure-Activity Relationship, Tropanes",

author = "Cha, {Joo Hwan} and Mu-Fa Zou and Adkins, {Erika M} and Rasmussen, {S{\o}ren G F} and Loland, {Claus Juul} and Bernhard Schoenenberger and Ulrik Gether and Newman, {Amy Hauck}",

year = "2005",

month = dec,

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doi = "10.1021/jm050431y",

language = "English",

volume = "48",

pages = "7513--6",

journal = "Journal of Medicinal Chemistry",

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TY - JOUR

T1 - Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

AU - Cha, Joo Hwan

AU - Zou, Mu-Fa

AU - Adkins, Erika M

AU - Rasmussen, Søren G F

AU - Loland, Claus Juul

AU - Schoenenberger, Bernhard

AU - Gether, Ulrik

AU - Newman, Amy Hauck

PY - 2005/12/1

Y1 - 2005/12/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Cercopithecus aethiops

KW - Cocaine

KW - Dopamine Plasma Membrane Transport Proteins

KW - Fluorescent Dyes

KW - Humans

KW - Microscopy, Confocal

KW - Norepinephrine Plasma Membrane Transport Proteins

KW - Rhodamines

KW - Serotonin Plasma Membrane Transport Proteins

KW - Structure-Activity Relationship

KW - Tropanes

U2 - 10.1021/jm050431y

DO - 10.1021/jm050431y

M3 - Journal article

C2 - 16302792

SN - 0022-2623

VL - 48

SP - 7513

EP - 7516

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 24

ER -

Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

Abstract

Keywords

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