Keller, Max and Kuhn, Kilian K. and Einsiedel, Juergen and Huebner, Harald and Biselli, Sabrina and Mollereau, Catherine and Wifling, David and Svobodova, Jaroslava and Bernhardt, Guenther and Cabrele, Chiara and Vanderheyden, Patrick M. L. and Gmeiner, Peter and Buschauer, Armin (2016) Mimicking of Arginine by Functionalized N-omega-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples. JOURNAL OF MEDICINAL CHEMISTRY, 59 (5). pp. 1925-1945. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N-terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of-concept study. The N-omega-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with K-i values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACYLGUANIDINE BIOISOSTERIC APPROACH; G-PROTEIN; Y-4 RECEPTOR; SELECTIVE AGONISTS; PICOMOLAR AFFINITY; PHOSPHOLIPASE-C; AT(1) RECEPTORS; RGD PEPTIDES; SIDE-CHAIN; ANTAGONISTS; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2019 09:23 |
| Last Modified: | 26 Mar 2019 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3251 |
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