| (S)- and (R)-Fluoxetine as Native Markers in Mass Spectrometry (MS) Binding Assays Addressing the Serotonin Transporter. | |
| | |
MedLine Citation:
|
PMID: 21793219 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A recently established and validated LC-ESI-MS/MS method for quantification of fluoxetine was used to implement MS binding assays for the human serotonin transporter (hSERT)-the primary target in the treatment of depression and emotional disorders. As a label-free screening technique, MS binding assays offer the opportunity to perform kinetic, saturation and competition assays using both (S)- and (R)-fluoxetine as native markers. In kinetic experiments, an association rate constant (k(+1) ) of 0.92±0.17×10(6) M(-1) s(-1) and a dissociation rate constant (k(-1) ) of 0.0032±0.0002 s(-1) for (S)-fluoxetine binding to hSERT were determined. Saturation experiments provided K(d) values of 4.4±0.4 nM and 5.2±0.9 nM for (S)- and (R)-fluoxetine, respectively; statistical analysis revealed that the two enantiomers are equipotent. In competitive experiments with (S)-fluoxetine as a marker, K(i) values were obtained for various known inhibitors with a broad range of affinities for hSERT that correlate well with literature data obtained from radioligand binding experiments with [(3) H]imipramine. Additional competitive experiments using (R)-fluoxetine as a marker led to K(i) values for SERT inhibitors that deviate only marginally from those determined using the (S)-enantiomer. No changes in the rank order of affinities occurred, indicating that there is no difference in the binding characteristics of the two enantiomers. |
| | |
Authors:
|
Marielle Hess; Georg Höfner; Klaus T Wanner |
Related Documents
:
|
16573699 - Coactivation of vibrio vulnificus putap operon by camp receptor protein and putr throug... 11112289 - An erp investigation of binding and coreference. 19037309 - Gibberellin-induced della recognition by the gibberellin receptor gid1. 9696769 - Fnr, narp, and narl regulation of escherichia coli k-12 napf (periplasmic nitrate reduc... 18486609 - Phosphoethanolamine-complexed c-reactive protein: a pharmacological-like macromolecule ... 1328649 - Camp-crp activator complex and the cytr repressor protein bind co-operatively to the cy... 21816169 - Structural insight into the low affinity between thermotoga maritima chea and cheb comp... 10215509 - Effects of chronic administration of interferon alpha a/d on serotonergic receptors in ... 22536379 - Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservati... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-7-26 |
Journal Detail:
|
Title: ChemMedChem Volume: - ISSN: 1860-7187 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-7-27 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101259013 Medline TA: ChemMedChem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
|
Department Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstr. 7, 81377 München (Germany). |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Regulating iron storage and metabolism with RNA: an overview of posttranscriptional controls of intr...
Next Document: Preparation and Antitumour Properties of the Enantiomers of a Hypoxia-Selective Nitro Analogue of th...