Design of triazole-stapled BCL9 α-helical peptides to target the β-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction.

ABSTRACT: The interaction between β-catenin and B-cell CLL/lymphoma 9 (BCL9), critical for the transcriptional activity of β-catenin, is mediated by a helical segment from BCL9 and a large binding groove in β-catenin. Design of potent, metabolically stable BCL9 peptides represents an attractive approach to inhibit the activity of β-catenin. In this study, we report the use of the Huisgen 1,3-dipolar cycloaddition reaction to generate triazole-stapled BCL9 α-helical peptides. The high efficiency and mild conditions of this "click" reaction combined with the ease of synthesis of the necessary unnatural amino acids allows for facile synthesis of triazole-stapled peptides. We have performed extensive optimization of this approach and identified the optimal combinations of azido and alkynyl linkers neces

SUBMITTER: Kawamoto SA 

PROVIDER: S-EPMC3286869 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature