Mimicking of Arginine by Functionalized N(ω)-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.

Keller M, Kuhn KK, Einsiedel J, Hübner H, Biselli S, Mollereau C, Wifling D, Svobodová J, Bernhardt G, Cabrele C, Vanderheyden PML, Gmeiner P, Buschauer A (2016)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2016

Journal

Journal of Medicinal Chemistry American Chemical Society

Book Volume: 59

Pages Range: 1925-45

Journal Issue: 5

DOI: 10.1021/acs.jmedchem.5b01495

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(ω)-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 Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.

Authors with CRIS profile

Jürgen Einsiedel Lehrstuhl für Pharmazeutische Chemie Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

Involved external institutions

Universität Regensburg DE Germany (DE) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) FR France (FR) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Vrije Universiteit Brussel (VUB) BE Belgium (BE)

How to cite

APA:

Keller, M., Kuhn, K.K., Einsiedel, J., Hübner, H., Biselli, S., Mollereau, C.,... Buschauer, A. (2016). Mimicking of Arginine by Functionalized N(ω)-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), 1925-45. https://dx.doi.org/10.1021/acs.jmedchem.5b01495

MLA:

Keller, Max, et al. "Mimicking of Arginine by Functionalized N(ω)-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 (2016): 1925-45.

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