2. Academic Validation
  3. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

  • Chembiochem. 2016 Apr 15;17(8):689-92. doi: 10.1002/cbic.201500648.
Yuteng Wu 1,  Lasse B Olsen 1,  Yu Heng Lau 1,  Claus Hatt Jensen 1,  Maxim Rossmann 2,  Ysobel R Baker 1,  Hannah F Sore 1,  Súil Collins 1,  David R Spring 3
Affiliations

Affiliations

  • 1 University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
  • 2 Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
  • 3 University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. spring@ch.cam.ac.uk.
PMID: 26919579 DOI: 10.1002/cbic.201500648
Abstract

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.

Keywords

MDM2; click chemistry; linker; photoaffinity labeling; stapled peptide.

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