(±)-2-(N-tert-Butylamino)-3′-[125I]-iodo-4′-azidopropiophenone: A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban)
- Resource Type
- Article
- Authors
- Lapinsky, David J.; Aggarwal, Shaili; Nolan, Tammy L.; Surratt, Christopher K.; Lever, John R.; Acharya, Rejwi; Vaughan, Roxanne A.; Pandhare, Akash; Blanton, Michael P.
- Source
- Bioorganic & Medicinal Chemistry Letters. Jan2012, Vol. 22 Issue 1, p523-526. 4p.
- Subject
- *DOPAMINE
*ANTIDEPRESSANTS
*NICOTINIC receptors
*LIGANDS (Biochemistry)
*PHOTOAFFINITY labeling
*CELL culture
- Language
- ISSN
- 0960-894X
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. [Copyright &y& Elsevier]