Synthesis and biological evaluation of cyclic and branched peptide analogues as ligands for cholecystokinin type 1 receptor

Stefania De Luca, Antonia De Capua, Michele Saviano, Raffaella Della Moglie, Luigi Aloj, Laura Tarallo, Carlo Pedone, Giancarlo Morelli

Research output: Contribution to journalArticle

Abstract

A library of cyclic CCK8 analogues, containing unnatural amino acids in the peptide sequence, is prepared using solid-phase synthesis. The structure of these cyclic peptides is based on a previously synthesised compound, cyclo-CCK8, selective for CCK1 receptor. Structure-activity investigations are performed by evaluating the binding properties of the new analogues. In particular, the binding ability of the cyclic CCK8 analogues is tested by nuclear medicine studies on cell line transfected with CCK1 receptor. Compounds named cyclo-A4-cyclo-A7 show binding constant in the range 6.0-8.0 μM, with an improved affinity over the previous described cyclo-CCK8, but almost comparable IC50 values among new analogues towards CCK1 were obtained.

Original languageEnglish
Pages (from-to)5845-5853
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number17
DOIs
Publication statusPublished - Sep 1 2007

    Fingerprint

Keywords

  • Cholecystokinin
  • Cyclic constraints
  • Cyclic peptides
  • Receptor binding affinity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this