English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The all-hydrocarbon peptide stapling strategy has recently been extensively explored in drug discovery. There remains the potential for improvement regarding the retention of the amino acid side chains at the stapled positions. Herein, we describe a new series of amino acids that not only contain the native side chains, but also carry the alkenyl arms that are needed for the ring-closing stapling chemistry. We incorporate the new amino acids into a β-catenin-binding domain of Axin (469-482) and develop a new category of stapled peptides with the retention of the native side chains. These stapled peptides exhibit high α-helicity, strong proteolytic stability and good cell permeability. Biochemical experiments demonstrate that these stapled peptides can activate β-catenin more efficiently than canonical stapled peptides due to the presence of extra side chains. We expect that the new side-chain-retention stapling method would expand the scope of the all-hydrocarbon stapled peptide strategy by retaining some important peripheral residues for protein-protein interactions or preserving key hydrophilic side chains to improve solubility.

A novel peptide stapling strategy enables the retention of ring-closing amino acid side chains for the Wnt/β-catenin signalling pathway