Gienger, Marie and Huebner, Harald and Loeber, Stefan and Koenig, Burkhard and Gmeiner, Peter (2020) Structure-based development of caged dopamine D-2/D-3 receptor antagonists. SCIENTIFIC REPORTS, 10 (1). ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Dopamine is a neurotransmitter of great physiological relevance. Disorders in dopaminergic signal transduction are associated with psychiatric and neurological pathologies such as Parkinson's disease, schizophrenia and substance abuse. Therefore, a detailed understanding of dopaminergic neurotransmission may provide access to novel therapeutic strategies for the treatment of these diseases. Caged compounds with photoremovable groups represent molecular tools to investigate a biological target with high spatiotemporal resolution. Based on the crystal structure of the D-3 receptor in complex with eticlopride, we have developed caged D-2/D-3 receptor ligands by rational design. We initially found that eticlopride, a widely used D-2/D-3 receptor antagonist, was photolabile and therefore is not suitable for caging. Subtle structural modification of the pharmacophore led us to the photostable antagonist dechloroeticlopride, which was chemically transformed into caged ligands. Among those, the 2-nitrobenzyl derivative 4 (MG307) showed excellent photochemical stability, pharmacological behavior and decaging properties when interacting with dopamine receptor-expressing cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHOTOREMOVABLE PROTECTING GROUPS; ANTIDOPAMINERGIC PROPERTIES; RELEASE AUTOINHIBITION; REACTION-MECHANISMS; RAPID RELEASE; D-3; CHEMISTRY; DISCOVERY; MODULATION; CHELATORS; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2021 07:25 |
| Last Modified: | 09 Apr 2021 07:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45331 |
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