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Journal Article

Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons80398

Kirmeier,  Thomas
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80341

Gopalakrishnan,  Ranganath
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80332

Ganal,  Vanessa
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons199818

Werner,  Anna Maria
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80290

Cuboni,  Serena
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80515

Schmidt,  Ulrike
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80372

Holsboer,  Florian
Emeritiertes wissenschaftliches Mitglied, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80489

Rein,  Theo
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80356

Hausch,  Felix
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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journal.pone.0148608.PDF
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Citation

Kirmeier, T., Gopalakrishnan, R., Ganal, V., Werner, A. M., Cuboni, S., Rudolf, G. C., et al. (2016). Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores. PLOS ONE, 11(2): e0148608. doi:10.1371/journal.pone.0148608.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-119E-C
Abstract
The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes.