Design and synthesis of efficient fluororethylene-peptidomimetic inhibitors of dipeptidyl peptidase III (DPP3)

Harald Podversnik, Shalinee Jha, Peter Macheroux, Rolf Breinbauer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Dipeptidyl peptidase III (DPP3) is a ubiquitously expressed zinc-dependent peptide cutting enzyme and selectively hydrolyses amide bonds to cleave N-terminal dipeptide fragments off of physiologically important oligopeptides. DPP3 has been found in a multitude of different types of cells and appears to be involved in various physiological processes (e.g. nociception, blood pressure control, protein turnover). Using the slowly converted peptide substrate tynorphin (VVYPW) as starting point, we have replaced the scissile bond with a fluoroethylene bioisostere to design ground state inhibitors, which led to the so far most effective peptide-based inhibitor of DPP3.

Original languageEnglish
Article number116831
JournalBioorganic and Medicinal Chemistry
Volume67
DOIs
Publication statusPublished - 1 Aug 2022

Keywords

  • Bioisostere
  • Metalloenzyme
  • Peptidomimetic
  • Protease
  • Small molecule inhibitor

ASJC Scopus subject areas

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

Fields of Expertise

  • Human- & Biotechnology

Cooperations

  • BioTechMed-Graz

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