Binding-induced fluorescence of serotonin transporter ligands: A spectroscopic and structural study of 4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP(+)) and APP(+) analogues.
The binding-induced fluorescence of 4-(4-(dimethylamino)-phenyl)-1-methylpyridinium (APP(+)) and two new serotonin transporter (SERT)-binding fluorescent analogues, 1-butyl-4-[4-(1-dimethylamino)phenyl]-pyridinium bromide (BPP(+)) and 1-methyl-4-[4-(1-piperidinyl)phenyl]-pyridinium (PPP(+)), has been investigated. Optical spectroscopy reveals that these probes are highly sensitive to their chemical microenvironment, responding to variations in polarity with changes in transition energies and responding to changes in viscosity or rotational freedom with emission enhancements. Molecular docking calculations reveal that the probes are able to access the nonpolar and conformationally restrictive binding pocket of SERT. As a result, the probes exhibit previously not identified binding-induced turn-on emission that is spectroscopically distinct from dyes that have accumulated intracellularly. Thus, binding and transport dynamics of SERT ligands can be resolved both spatially and spectroscopically.
Department of Chemistry, University of Miami , Coral Gables, Florida 33124, United States.
James N
JN
Wilson
Lucy Kate
LK
Ladefoged
W Michael
WM
Babinchak
Birgit
B
Schiøtt
D000814:Aniline Compounds / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011726:Pyridinium Compounds / Q000737:chemistry*; D012701:Serotonin / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D013050:Spectrometry, Fluorescence / Q000379:methods*
C572632:4-(4-(dimethylamino)phenyl)-1-methylpyridinium; D000814:Aniline Compounds; D011726:Pyridinium Compounds; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin