PuSH - Publication Server of Helmholtz Zentrum München: Development of novel PEX5-PEX14 protein-protein interaction (PPI) inhibitors based on an oxopiperazine template.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Marciniak, M.* ; Mroz, P.* ; Napolitano, V. ; Kalel, V.C.* ; Fino, R. ; Pykacz, E.* ; Schliebs, W.* ; Plettenburg, O. ; Erdmann, R.* ; Sattler, M. ; Popowicz, G.M. ; Dawidowski, M.*

Development of novel PEX5-PEX14 protein-protein interaction (PPI) inhibitors based on an oxopiperazine template.

Eur. J. Med. Chem. 258:115587 (2023)

Publ. Version/Full Text

DOI

PMC

	Open Access Gold (Paid Option)

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Oxopiperazine ; Peptidomimetics ; Protein-protein Interaction Inhibitors ; Structure-based Drug Design ; Trypanocidal Inhibitors ; α-helical Mimetics; Import; Pex14; Design

ISSN (print) / ISBN 0223-5234

e-ISSN 1768-3254

Journal European Journal of Medicinal Chemistry

Quellenangaben Volume: 258, Article Number: 115587

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Structural Biology (STB)
Institute of Medicinal Chemistry (IMC)

Grants Bundesministerium fuer Bildung and Forschung
Deutsche Forschungsgemeinschaft
Narodowe Centrum Nauki