(±)-2-(N-tert-Butylamino)-3′-[ 125I]-iodo-4′- azidopropiophenone: A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban)

David J. Lapinsky, Shaili Aggarwal, Tammy L. Nolan, Christopher K. Surratt, John R. Lever, Rejwi Acharya, Roxanne A. Vaughan, Akash Pandhare, Michael P. Blanton

Research output: Research - peer-reviewArticle

Abstract

Towards addressing the knowledge gap of how bupropion interacts with the dopamine transporter (DAT) and nicotinic acetylcholine receptors (nAChRs), a ligand was synthesized in which the chlorine of bupropion was isosterically replaced with an iodine and a photoreactive azide was added to the 4′-position of the aromatic ring. Analog (±)-3 (SADU-3-72) demonstrated modest DAT and α4β2 nAChR affinity. A radioiodinated version was shown to bind covalently to hDAT expressed in cultured cells and affinity-purified, lipid-reincorporated human α4β2 neuronal nAChRs. Co-incubation of (±)-[ 125I]-3 with non-radioactive (±)-bupropion or (-)-cocaine blocked labeling of these proteins. Compound (±)-[ 125I]-3 represents the first successful example of a DAT and nAChR photoaffinity ligand based on the bupropion scaffold. Such ligands are expected to assist in mapping bupropion-binding pockets within plasma membrane monoamine transporters and ligand-gated nAChR ion channels.

LanguageEnglish (US)
Pages523-526
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Bupropion
Dopamine Plasma Membrane Transport Proteins
Nicotinic Receptors
Ligands
2-(N-tert-butylamino)-3'-iodo-4'-azidopropiophenone
Azides
Chlorine
Cell membranes
Ion Channels
Cocaine
Scaffolds
Iodine
Labeling
Cells
Lipids
Proteins
Ligand-Gated Ion Channels
Membrane Transport Proteins
Cultured Cells
Cell Membrane

Keywords

  • Bupropion
  • Dopamine transporter
  • Nicotinic acetylcholine receptor
  • Photoaffinity labeling

ASJC Scopus subject areas

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

Cite this

(±)-2-(N-tert-Butylamino)-3′-[ 125I]-iodo-4′- azidopropiophenone : A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban). / Lapinsky, David J.; Aggarwal, Shaili; Nolan, Tammy L.; Surratt, Christopher K.; Lever, John R.; Acharya, Rejwi; Vaughan, Roxanne A.; Pandhare, Akash; Blanton, Michael P.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 1, 01.01.2012, p. 523-526.

Research output: Research - peer-reviewArticle

Lapinsky, David J. ; Aggarwal, Shaili ; Nolan, Tammy L. ; Surratt, Christopher K. ; Lever, John R. ; Acharya, Rejwi ; Vaughan, Roxanne A. ; Pandhare, Akash ; Blanton, Michael P./ (±)-2-(N-tert-Butylamino)-3′-[ 125I]-iodo-4′- azidopropiophenone : A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban). In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 1. pp. 523-526
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