Evolution of a Compact Photoprobe for the Dopamine Transporter Based on (±)-threo-Methylphenidate.
ACS Med Chem Lett
; 3(5): 378-382, 2012 May 10.
Article
en En
| MEDLINE
| ID: mdl-23066448
ABSTRACT
The development of photoaffinity ligands for determining covalent points of attachment to the dopamine transporter (DAT) has predominantly focused on tropane-based compounds bearing variable-length linkers between the photoreactive group and inhibitor pharmacophore. In order to expand the array of photoprobes useful for mapping inhibitor-binding pockets within the DAT, a compact non-tropane ligand was synthesized featuring a photoreactive azide and iodine tag directly attached to the aromatic ring of (±)-threo-methylphenidate. (±)-threo-4-Azido-3-iodomethylphenidate ((±)-6); K(i) = 4.0 ± 0.8 nM) displayed high affinity for hDAT. Moreover, a radioiodinated analog of (±)-6 demonstrated covalent ligation to the DAT in cultured cells and rat striatal membranes, thus suggesting the potential utility of this photoprobe in DAT structure-function studies.
Texto completo:
1
Banco de datos:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos