Ertl, Fabian J. and Friedel, Anna and Schmid, Elena J. and Hoering, Carina and Archipowa, Nataliya and Koch, Pierre and Maschauer, Simone and Kutta, Roger J. and Prante, Olaf and Keller, Max (2025) High-Affinity and Proteolytically Stable Peptidic Fluorescent NTS1R Ligands. JOURNAL OF MEDICINAL CHEMISTRY, 68 (18). pp. 19482-19502. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
Labeled ligands for the neurotensin receptor 1 (NTS1R), which is expressed in the CNS, the gastrointestinal tract, and in malignant tumors, are needed to investigate NTS1R-ligand binding and NTS1R expression. Aiming for fluorescence-labeled neurotensin(8-13)-derived NTS1R ligands with high affinity and proteolytic stability, several previous approaches were combined: (1) replacement of Arg8 by an amino-functionalized carbamoylated arginine, allowing conjugation to a fluorophore, (2) N alpha-methylation of Arg8 and replacement of Tyr by beta,beta-dimethyl-l-Tyr11, conferring proteolytic stability, and (3) replacement of Leu13 by trimethylsilyl-Ala, boosting binding affinity. This strategy gave fluorescent NTS1R ligands with unprecedented NTS1R binding affinity (5-TAMRA-labeled ligand 19: K i 0.14 nM, sulfo-Cy5-labeled probe 21: K i 0.094 nM) and high stability in human plasma (t 1/2 >> 48 h). Their suitability for competition binding studies (flow cytometry; 19, 21) and the imaging of NTS1R expression in living cells (confocal microscopy, biomolecular imaging; 19, 21) and tumor tissue (biomolecular imaging; 21) is demonstrated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEUROTENSIN RECEPTOR; NEUROPEPTIDE-Y; BINDING; ANALOGS; (L)-(TRIMETHYLSILYL)ALANINE; SITE |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jun 2026 07:53 |
| Last Modified: | 18 Jun 2026 07:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66572 |
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