Elisabetta Scalia
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
Antony Chirco
Lorenzo Calugi
Elena Lenci
Patrick J. Pagano
Dr Giordano Pula G.Pula@hull.ac.uk
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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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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