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Development of New Peptidomimetic NADPH Oxidase Inhibitors with Antithrombotic Properties

Scalia, Elisabetta; Chirco, Antony; Calugi, Lorenzo; Lenci, Elena; Pagano, Patrick J.; Pula, Giordano; Trabocchi, Andrea

Authors

Elisabetta Scalia

Antony Chirco

Lorenzo Calugi

Elena Lenci

Patrick J. Pagano

Andrea Trabocchi



Abstract

The ability of synthetic peptides inhibitors of NOX1 to effectively block the production of ROS by the enzyme was studied with different methodologies. Specifically, taking advantage of our understanding of the active epitope of the regulatory NOX1 subunit NOXA1 as a potent inhibitor of NOX1-derived O2⋅− formation, a panel of peptidomimetic derivatives of this peptide were designed and synthesized with the aim of improving their activity and increasing their stability in plasma. The results highlighted that improved efficacy and potency was found for both the peptide-peptoid hybrid GS2, whereas stapled peptide AC5 and its precursor showed higher stability despite lower biological potency. This study showed that minimal structural modifications of NOXA1 peptides are required to improve both their potency and stability to finally achieve best candidates as new potential anti-thrombotic drugs.

Citation

Scalia, E., Chirco, A., Calugi, L., Lenci, E., Pagano, P. J., Pula, G., & Trabocchi, A. (2024). Development of New Peptidomimetic NADPH Oxidase Inhibitors with Antithrombotic Properties. ChemMedChem, 19(19), Article e202400330. https://doi.org/10.1002/cmdc.202400330

Journal Article Type Article
Acceptance Date Jun 26, 2024
Online Publication Date Jun 26, 2024
Publication Date Oct 1, 2024
Deposit Date Mar 6, 2025
Publicly Available Date Mar 7, 2025
Journal ChemMedChem
Print ISSN 1860-7179
Electronic ISSN 1860-7187
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 19
Issue 19
Article Number e202400330
DOI https://doi.org/10.1002/cmdc.202400330
Keywords Drug discovery; NADPH oxidase; Peptides; Reactive oxygen species; Cardiovascular diseases
Public URL https://hull-repository.worktribe.com/output/4788946

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.





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