NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids

Beitrag in einer Fachzeitschrift

Details zur Publikation

Autor(en): Simeth NA, Bause M, Dobmeier M, Kling R, Lachmann D, Hübner H, Einsiedel J, Gmeiner P, Koenig B
Zeitschrift: Bioorganic & Medicinal Chemistry
Jahr der Veröffentlichung: 2017
Band: 25
Heftnummer: 1
Seitenbereich: 350-359
ISSN: 0968-0896


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.

FAU-Autoren / FAU-Herausgeber

Einsiedel, Jürgen Dr.
Lehrstuhl für Pharmazeutische Chemie
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Kling, Ralf
Lehrstuhl für Pharmazeutische Chemie

Zusätzliche Organisationseinheit(en)
Emil-Fischer-Zentrum (Emil Fischer Center)

Autor(en) der externen Einrichtung(en)
Universität Regensburg


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

Simeth, Nadja A., et al. "NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids." Bioorganic & Medicinal Chemistry 25.1 (2017): 350-359.


Zuletzt aktualisiert 2018-28-06 um 23:23