Chemical Synthesis of Hydrocarbon-Stapled Peptides for Protein Interaction Research and Therapeutic Targeting
Published Online: 1 SEP 2011
Copyright © 2011 by John Wiley and Sons, Inc.
Lab Protocol Title
Current Protocols in Chemical Biology
How to Cite
Bird, G. H., Christian Crannell, W. and Walensky, L. D. 2011. Chemical Synthesis of Hydrocarbon-Stapled Peptides for Protein Interaction Research and Therapeutic Targeting. Current Protocols in Chemical Biology. 3:99–117.
- Published Online: 1 SEP 2011
- Published Print: SEP 2011
The peptide α-helix represents one of nature's most featured protein shapes and is employed in a diversity of protein architectures, from the cytoskeletal infrastructure to the most intimate contact points between crucial signaling proteins. By installing an all-hydrocarbon crosslink into native sequences, the shape and biological activity of natural peptide α-helices can be recapitulated, yielding a chemical toolbox that can be used both to interrogate the protein interactome and to modulate interaction networks for potential therapeutic benefit. Here, current methodology for synthesizing stabilized α-helices (SAH) corresponding to key protein interaction domains is described. A stepwise approach is taken for the production of crosslinking non-natural amino acids, incorporation of the residues into peptide templates, and application of ruthenium-catalyzed ring-closing metathesis to generate hydrocarbon-stapled peptides. Through facile derivatization and functionalization steps, SAHs can be tailored for a broad range of applications in biochemical, structural, proteomic, cellular, and in vivo studies. Curr. Protoc. Chem. Biol. 3:99-117 © 2011 by John Wiley & Sons, Inc.
- hydrocarbon stapling;
- olefin metathesis;
- protein interaction;