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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	48
Udgave nummer	24
Sider (fra-til)	7513-6
Antal sider	4
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm050431y
Status	Udgivet - 1 dec. 2005

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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,

day = "1",

doi = "10.1021/jm050431y",

language = "English",

volume = "48",

pages = "7513--6",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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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

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