Synthesis, biological activity and resistance to proteolytic digestion of new cyclic dermorphin/deltorphin analogues

Krzysztof Bańkowski, Ewa Witkowska, Olga M. Michalak, Katarzyna Sidoryk, Ewa Szymanek, Bozena Antkowiak, Małgorzata Paluch, Katarzyna E. Filip, Marek Cebrat, Bartosz Setner, Zbigniew Szewczuk, Piotr Stefanowicz, Piotr Cmoch, Jan Izdebski

Research output: Contribution to journalArticlepeer-review

Abstract

A series of novel cyclic ureidopeptides, analogues of dermorphine/ deltorphine tetrapeptide, were synthesized by solid phase peptide synthesis and/or in solution. The antinociceptive activity of N-substituted amides 1-10 was evaluated using hot-plate and tail-flick tests. Analogue 1 showed significant, stronger than morphine, antinociceptive effect after systemic applications. All analogues were also tested for their in vitro resistance to proteolysis by means of mass spectroscopy and it was found that all substituted amides 1-10 showed full stability during incubation with large excess of chymotrypsin and pepsin. Compound 1 is a lead molecule for further evaluation.

Original languageEnglish (US)
Pages (from-to)457-467
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume63
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Antinociceptive effect
  • Cyclic opioid peptides
  • Dermorphin/deltorphin analogues
  • Peptide synthesis
  • Stability to proteolytic enzymes

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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