• Max Keller
  • Kilian K Kuhn
  • Jürgen Einsiedel
  • Harald Hübner
  • Sabrina Biselli
  • Catherine Mollereau
  • David Wifling
  • Jaroslava Svobodová
  • Günther Bernhardt
  • Chiara Cabrele
  • Patrick M L Vanderheyden
  • Peter Gmeiner
  • Armin Buschauer

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.

Original languageEnglish
Pages (from-to)1925-1945
Number of pages21
JournalJournal of Medicinal Chemistry
Issue number5
Publication statusPublished - 2016

    Research areas

  • Angiotensin II, Arginine, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Ligands, Molecular Structure, Neuropeptide Y, Neurotensin, Oligopeptides, Peptide Fragments, Receptors, Angiotensin, Receptors, Neuropeptide, Receptors, Neurotensin, Structure-Activity Relationship, Research Support, Non-U.S. Gov't

ID: 30528188