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Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling
Author(s) -
Wu Yuteng,
Olsen Lasse B.,
Lau Yu Heng,
Jensen Claus Hatt,
Rossmann Maxim,
Baker Ysobel R.,
Sore Hannah F.,
Collins Súil,
Spring David R.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500648
Subject(s) - linker , benzophenone , peptide , chemistry , click chemistry , photoaffinity labeling , combinatorial chemistry , labelling , target peptide , peptide sequence , biochemistry , biophysics , binding site , biology , organic chemistry , computer science , gene , operating system
Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo‐crosslinking motif and a peptide stapling reagent. Using double‐click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo‐crosslinking amino acid. When applied to a p53‐derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull‐down assays, and can be used to investigate the target selectivity of stapled peptides.