Simeth, Nadja A. and Bause, Manuel and Dobmeier, Michael and Kling, Ralf C. and Lachmann, Daniel and Huebner, Harald and Einsiedel, Juergen and Gmeiner, Peter and Koenig, Burkhard (2017) NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids. BIOORGANIC & MEDICINAL CHEMISTRY, 25 (1). pp. 350-359. ISSN 0968-0896, 1464-3391
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHASE PEPTIDE-SYNTHESIS; RECEPTOR-BINDING; FUNCTIONAL EXPRESSION; LIGAND-BINDING; G-PROTEIN; ANALOGS; CANCER; AFFINITY; SITE; BIODISTRIBUTION; Neurotensin; Peptides; Non-natural amino acid |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:57 |
| Last Modified: | 19 Feb 2019 07:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/61 |
Actions (login required)
 |
View Item |
