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

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

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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.
Original languageEnglish
Article numbere24158
Number of pages10
JournalPeptide Science
Early online date24 Mar 2020
Publication statusE-pub ahead of print - 24 Mar 2020


  • Alzheimer disease
  • ubiquitin
  • staples

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