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Design, synthesis and evaluation of E2‐25K derived stapled peptides
Author(s) -
Watson Morag E.,
Scott Daniel,
Jamieson Craig,
Layfield Robert,
Mason Andrew M.
Publication year - 2021
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 7
ISSN - 2475-8817
DOI - 10.1002/pep2.24158
Subject(s) - ubiquitin , peptide , in vitro , chemistry , mutant , computational biology , biophysics , combinatorial chemistry , microbiology and biotechnology , biochemistry , biology , gene
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.