A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone

David J. Lapinsky; Shaili Aggarwal; Yurong Huang; Christopher K. Surratt; John R. Lever; James D. Foster; Roxanne A. Vaughan

doi:10.1016/j.bmc.2009.04.057

A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone

David J. Lapinsky, Shaili Aggarwal, Yurong Huang, Christopher K. Surratt, John R. Lever, James D. Foster, Roxanne A. Vaughan

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored in contrast to tropane-based compounds such as cocaine. In order to fill this knowledge gap, a ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group. The analog 1-(4-azido-3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one demonstrated appreciable binding affinity for the DAT (K_i = 78 ± 18 nM), suggesting the potential utility of a radioiodinated version in structure-function studies of this protein.

Original language	English (US)
Pages (from-to)	3770-3774
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	11
DOIs	https://doi.org/10.1016/j.bmc.2009.04.057
State	Published - Jun 1 2009
Externally published	Yes

Keywords

Cocaine
Dopamine transporter
Photoaffinity labeling
Pyrovalerone

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2009.04.057

Cite this

@article{a8994e5cee2248ef8a5daffd96b832b7,

title = "A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone",

abstract = "Non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored in contrast to tropane-based compounds such as cocaine. In order to fill this knowledge gap, a ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group. The analog 1-(4-azido-3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one demonstrated appreciable binding affinity for the DAT (Ki = 78 ± 18 nM), suggesting the potential utility of a radioiodinated version in structure-function studies of this protein.",

keywords = "Cocaine, Dopamine transporter, Photoaffinity labeling, Pyrovalerone",

author = "Lapinsky, {David J.} and Shaili Aggarwal and Yurong Huang and Surratt, {Christopher K.} and Lever, {John R.} and Foster, {James D.} and Vaughan, {Roxanne A.}",

note = "Funding Information: This work was funded by a Hunkele Dreaded Disease Award (D.J.L.), the Mylan School of Pharmacy at Duquesne University (D.J.L.), and NIH Grants DA16604 (C.K.S.) and DA15175 (R.A.V.). We thank NIDA Drug Supply for contribution of certain nonradioactive DAT ligand compounds.",

year = "2009",

month = jun,

day = "1",

doi = "10.1016/j.bmc.2009.04.057",

language = "English (US)",

volume = "17",

pages = "3770--3774",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "11",

}

TY - JOUR

T1 - A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone

AU - Lapinsky, David J.

AU - Aggarwal, Shaili

AU - Huang, Yurong

AU - Surratt, Christopher K.

AU - Lever, John R.

AU - Foster, James D.

AU - Vaughan, Roxanne A.

N1 - Funding Information: This work was funded by a Hunkele Dreaded Disease Award (D.J.L.), the Mylan School of Pharmacy at Duquesne University (D.J.L.), and NIH Grants DA16604 (C.K.S.) and DA15175 (R.A.V.). We thank NIDA Drug Supply for contribution of certain nonradioactive DAT ligand compounds.

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored in contrast to tropane-based compounds such as cocaine. In order to fill this knowledge gap, a ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group. The analog 1-(4-azido-3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one demonstrated appreciable binding affinity for the DAT (Ki = 78 ± 18 nM), suggesting the potential utility of a radioiodinated version in structure-function studies of this protein.

AB - Non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored in contrast to tropane-based compounds such as cocaine. In order to fill this knowledge gap, a ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group. The analog 1-(4-azido-3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one demonstrated appreciable binding affinity for the DAT (Ki = 78 ± 18 nM), suggesting the potential utility of a radioiodinated version in structure-function studies of this protein.

KW - Cocaine

KW - Dopamine transporter

KW - Photoaffinity labeling

KW - Pyrovalerone

UR - http://www.scopus.com/inward/record.url?scp=65649127839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649127839&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2009.04.057

DO - 10.1016/j.bmc.2009.04.057

M3 - Article

C2 - 19442525

AN - SCOPUS:65649127839

SN - 0968-0896

VL - 17

SP - 3770

EP - 3774

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 11

ER -

A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this