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

Autor: Wu Y; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Olsen LB; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Lau YH; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Jensen CH; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Rossmann M; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK., Baker YR; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Sore HF; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Collins S; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Spring DR; University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. spring@ch.cam.ac.uk.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2016 Apr 15; Vol. 17 (8), pp. 689-92. Date of Electronic Publication: 2016 Mar 16.
DOI: 10.1002/cbic.201500648
Abstrakt: 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.
(© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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