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

ABSTRACT: 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 th

SUBMITTER: Wu Y 

PROVIDER: S-EPMC5672839 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature