A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone.
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.
Lapinsky
David J
DJ
Division of Pharmaceutical Sciences, Duquesne University Mylan School of Pharmacy, 600 Forbes Avenue, Pittsburgh, PA 15282, USA. lapinskyd@duq.edu
Aggarwal
Shaili
S
Huang
Yurong
Y
Surratt
Christopher K
CK
Lever
John R
JR
Foster
James D
JD
Vaughan
Roxanne A
RA
D045744:Cell Line, Tumor; D050483:Dopamine Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D019920:Photoaffinity Labels; D011759:Pyrrolidines; C005719:pyrovalerone