Flexible fluorine-thiol displacement stapled peptides with enhanced membrane penetration for the estrogen receptor/coactivator interaction.

ABSTRACT: Understanding how natural and engineered peptides enter cells would facilitate the elucidation of biochemical mechanisms underlying cell biology and is pivotal for developing effective intracellular targeting strategies. In this study, we demonstrate that our peptide stapling technique, fluorine-thiol displacement reaction (FTDR), can produce flexibly constrained peptides with significantly improved cellular uptake, particularly into the nucleus. This platform confers enhanced flexibility, which is further amplified by the inclusion of a D-amino acid, while maintaining environment-dependent α helicity, resulting in highly permeable peptides without the need for additional cell-penetrating motifs. Targeting the estrogen receptor α (ERα)-coactivator interaction prevalent in estrogen receptor

SUBMITTER: Maloney R 

PROVIDER: S-EPMC11667158 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature