Stapled Peptide Inhibitors of Protein-Protein Interactions

Mathias Wendt, Niall McLoughlin, Tom Grossmann*

*Corresponding author for this work

Research output: Chapter in Book / Report / Conference proceedingChapterAcademic


Conformationally constrained α-helical peptides have become important tool molecules in Chemical Biology research. In particular, macrocyclic α-helical peptides that have been constrained via inter-side chain cross-links, so-called stapled peptides, found widespread applications and are considered promising scaffolds for therapeutic applications. Stapled peptides are usually obtained by standard solid-phase peptide synthesis and the introduction of at least two amino acids that allow subsequent macrocyclization. Macrocycles of diverse sizes, functionalities and, architectures can be generated and result in peptides with improved target affinity, proteolytic stability and in some cases, increased cell permeability. In this chapter, the general principles of stapled peptide design are discussed along with notable examples of both one- and two-component peptide stapling reactions. As an example, stapled peptides targeting the protein–protein interaction between the tumor suppressor p53 and MDM2/MDMX are summarized, highlighting the diversity and potential of available stapling approaches.
Original languageEnglish
Title of host publicationInhibitors of Protein-Protein Interactions
Subtitle of host publicationSmall Molecules, Peptides and Macrocycles
EditorsAli Tavassoli
Place of PublicationLondon
PublisherRoyal Society of Chemistry
Number of pages25
ISBN (Electronic)9781839160677
ISBN (Print)9781788015691
Publication statusPublished - 2021


Dive into the research topics of 'Stapled Peptide Inhibitors of Protein-Protein Interactions'. Together they form a unique fingerprint.

Cite this