Development of a Metabolically Stable Neurotensin Receptor 2 (NTS2) Ligand

Journal article
(Original article)


Publication Details

Author(s): Held C, Plomer M, Hübner H, Meltretter J, Pischetsrieder M, Gmeiner P
Journal: Chemmedchem
Publisher: Wiley-VCH Verlag
Publication year: 2013
Volume: 8
Journal issue: 1
Pages range: 75-81
ISSN: 1860-7179
Language: English


Abstract


Subtype-selective neurotensin receptor2 (NTS2) ligands can be used as molecular probes to investigate the physiological role of neurotensinergic systems and serve as lead compounds to initiate the development of drugs for the treatment of tonic pain. Starting from our recently described NTS2 ligand 1, structural variants of type 2 were synthesized to further improve binding affinity and selectivity to gain metabolic stability. The peptide-peptoid hybrid 2b showed excellent NTS2 binding affinity (K=2.8nM) and 22000-fold selectivity over NTS1, as well as metabolic stability over 32h in a serum degradation assay. Employing a MAPK-driven luciferase reporter gene assay and an IP accumulation assay, the neurotensin mimetic 2b displayed respective inhibitions of constitutive activity exceeding 4.3- and 3.9-fold that of the inverse agonist activity of the endogenous ligand neurotensin. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.



FAU Authors / FAU Editors

Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Held, Cornelia
Lehrstuhl für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Meltretter, Jasmin Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)
Pischetsrieder, Monika Prof. Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)
Plomer, Manuel
Lehrstuhl für Pharmazeutische Chemie


Additional Organisation
Emil-Fischer-Zentrum (Emil Fischer Center)


How to cite

APA:
Held, C., Plomer, M., Hübner, H., Meltretter, J., Pischetsrieder, M., & Gmeiner, P. (2013). Development of a Metabolically Stable Neurotensin Receptor 2 (NTS2) Ligand. Chemmedchem, 8(1), 75-81. https://dx.doi.org/10.1002/cmdc.201200376

MLA:
Held, Cornelia, et al. "Development of a Metabolically Stable Neurotensin Receptor 2 (NTS2) Ligand." Chemmedchem 8.1 (2013): 75-81.

BibTeX: 

Last updated on 2018-19-04 at 02:33