A Cell-Permeable Stapled Peptide Inhibitor of the Estrogen Receptor/Coactivator Interaction.

ABSTRACT: We and others have proposed that coactivator binding inhibitors, which block the interaction of estrogen receptor and steroid receptor coactivators, may represent a potential class of new breast cancer therapeutics. The development of coactivator binding inhibitors has been limited, however, because many of the current molecules which are active in in vitro and biochemical assays are not active in cell-based assays. Our goal in this work was to prepare a coactivator binding inhibitor active in cellular models of breast cancer. To accomplish this, we used molecular dynamics simulations to convert a high-affinity stapled peptide with poor cell permeability into R4K1, a cell-penetrating stapled peptide. R4K1 displays high binding affinity for estrogen receptor α, inhibits the formation of est

SUBMITTER: Speltz TE 

PROVIDER: S-EPMC6057476 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature