Design, synthesis and evaluation of E2-25K derived stapled peptides

Watson, Morag E.; Scott, Daniel; Jamieson, Craig; Layfield, Robert; Mason, Andrew M.

Abstract

© 2020 The Authors. Peptide Science published by Wiley Periodicals, Inc. Stabilised peptides are now established as potential drug candidates to probe previously intractable molecular targets, such as protein-protein interactions. Herein, we report the design and synthesis of eight short helical peptide analogues of the ubiquitin conjugating enzyme, E2-25K, as potential antagonists of the interaction between E2-25K and the Alzheimer's Disease (AD) associated ubiquitin mutant Ubb + 1. Biochemical evaluation revealed four putative antagonists of the Ubb + 1/E2-25K interaction that reduced incorporation of Ubb + 1 into polyubiquitin chains in vitro, validating the potential of this approach as a therapeutic strategy.

• Journal Article Type: Article
• Acceptance Date: Mar 6, 2020
• Online Publication Date: Mar 24, 2020
• Publication Date: 2021-01
• Deposit Date: Oct 20, 2021
• Publicly Available Date: Oct 20, 2021
• Journal: Peptide Science
• Electronic ISSN: 2475-8817
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 113
• Issue: 1
• Article Number: e24158
• DOI: https://doi.org/10.1002/pep2.24158
• Keywords: Organic Chemistry; Biomaterials; Biochemistry; Biophysics
• Public URL: https://nottingham-repository.worktribe.com/output/5308365
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/pep2.24158