Journal article
(Original article)


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


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.



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.

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