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

Watson, Morag E. and Scott, Daniel and Jamieson, Craig and Layfield, Robert and Mason, Andrew M. (2020) Design, synthesis and evaluation of E2-25K derived stapled peptides. Peptide Science. e24158. ISSN 2475-8817 (https://doi.org/10.1002/pep2.24158)

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Abstract

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.

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