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.
|Number of pages||10|
|Early online date||24 Mar 2020|
|Publication status||E-pub ahead of print - 24 Mar 2020|
- Alzheimer disease