(±)-2-(N-tert-Butylamino)-3′-[ 125I]-iodo-4′- azidopropiophenone: A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban)
Bioorganic and Medicinal Chemistry Letters
Bupropion, Dopamine transporter, Nicotinic acetylcholine receptor, Photoaffinity labeling
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. © 2011 Elsevier Ltd. All rights reserved.
Lapinsky, D., Aggarwal, S., Nolan, T., Surratt, C., Lever, J., Acharya, R., Vaughan, R., Pandhare, A., & Blanton, M. (2012). (±)-2-(N-tert-Butylamino)-3′-[ 125I]-iodo-4′- azidopropiophenone: A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban). Bioorganic and Medicinal Chemistry Letters, 22 (1), 523-526. https://doi.org/10.1016/j.bmcl.2011.10.086