NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids
Simeth NA, Bause M, Dobmeier M, Kling R, Lachmann D, Hübner H, Einsiedel J, Gmeiner P, Koenig B (2017)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2017
Journal
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Book Volume: 25
Pages Range: 350-359
Journal Issue: 1
DOI: 10.1016/j.bmc.2016.10.039
Abstract
Stimulation of the NTS2 neurotensin receptor causes antipsychotic effects and leads to a promotion of the l-opioid-independent antinociception, which is important in the modulation of tonic pain sensitivity. We report the synthesis and properties of a small library of peptidic agonists based on the active neurotensin fragment NT(8-13). Two tetrahydrofuran amino acid derivatives were synthesized to replace Tyr(11) in NT (8-13). Additionally, Arg(8), Arg(9), and Ile(12) of the lead peptide were exchanged by Lys, Lys, and Gly, respectively. The new compounds showed substantial NTS2 binding affinity and up to 1000-fold selectivity over NTS1. The highest selectivity (Ki(NTS2): 29 nM, Ki(NTS1): 35,000 nM) was observed for the peptide analog 17(Rtrans). (C) 2016 Elsevier Ltd. All rights reserved.
Authors with CRIS profile
Ralf Kling
Lehrstuhl für Pharmazeutische Chemie
Harald Hübner
Lehrstuhl für Pharmazeutische Chemie
Jürgen Einsiedel
Lehrstuhl für Pharmazeutische Chemie
Peter Gmeiner
Lehrstuhl für Pharmazeutische Chemie
Additional Organisation(s)
Involved external institutions
Germany (DE)How to cite
APA:
Simeth, N.A., Bause, M., Dobmeier, M., Kling, R., Lachmann, D., Hübner, H.,... Koenig, B. (2017). NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids. Bioorganic & Medicinal Chemistry, 25(1), 350-359. https://dx.doi.org/10.1016/j.bmc.2016.10.039
MLA:
Simeth, Nadja A., et al. "NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids." Bioorganic & Medicinal Chemistry 25.1 (2017): 350-359.
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