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Marciniak, Monika [Author]; Mróz, Piotr [Author]; Napolitano, Valeria [Author]; Kalel, Vishal C. [Author]; Fino, Roberto [Author]; Pykacz, Emilia [Author]; Schliebs, Wolfgang [Author]; Plettenburg, Oliver [Author]; Erdmann, Ralf [Author]; Sattler, Michael [Author]; Popowicz, Grzegorz M. [Author]; Dawidowski, Maciej [Author]

Development of novel PEX5-PEX14 protein-protein interaction (PPI) inhibitors based on an oxopiperazine template - [published Version]

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  • Media type: Text; E-Article
  • Title: Development of novel PEX5-PEX14 protein-protein interaction (PPI) inhibitors based on an oxopiperazine template
  • Contributor: Marciniak, Monika [Author]; Mróz, Piotr [Author]; Napolitano, Valeria [Author]; Kalel, Vishal C. [Author]; Fino, Roberto [Author]; Pykacz, Emilia [Author]; Schliebs, Wolfgang [Author]; Plettenburg, Oliver [Author]; Erdmann, Ralf [Author]; Sattler, Michael [Author]; Popowicz, Grzegorz M. [Author]; Dawidowski, Maciej [Author]
  • imprint: Amsterdam [u.a.] : Elsevier Science, 2023
  • Published in: European Journal of Medicinal Chemistry 258 (2023) ; European Journal of Medicinal Chemistry
  • Issue: published Version
  • Language: English
  • DOI: https://doi.org/10.15488/17278; https://doi.org/10.1016/j.ejmech.2023.115587
  • ISSN: 0223-5234
  • Keywords: Trypanocidal inhibitors ; Peptidomimetics ; α-Helical mimetics ; Protein-protein interaction inhibitors ; Structure-based drug design ; Oxopiperazine
  • Origination:
  • Footnote: Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen.
  • Description: Protein-protein interactions (PPIs) constitute an important but challenging class of molecular targets for small molecules. The PEX5-PEX14 PPI has been shown to play a critical role in glycosome biogenesis and its disruption impairs the metabolism in Trpanosoma parasites, eventually leading to their death. Therefore, this PPI is a potential molecular target for new drugs against diseases caused by Trypanosoma infections. Here, we report a new class of peptidomimetic scaffolds to target the PEX5-PEX14 PPI. The molecular design was based on an oxopiperazine template for the α-helical mimetics. A structural simplification along with modifications of the central oxopiperazine scaffold and addressing the lipophilic interactions led to the development of peptidomimetics that inhibit PEX5-TbPEX14 PPI and display cellular activity against T. b. brucei. This approach provides an alternative approach towards the development of trypanocidal agents and may be generally useful for the design of helical mimetics as PPI inhibitors.
  • Access State: Open Access
  • Rights information: Attribution - Non Commercial - No Derivs (CC BY-NC-ND)