Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase

Cellular uptake of circulating cholesterol occurs via the low density lipoprotein receptor (LDLR). The E3 ubiquitin ligase IDOL is a mediator of LDLR degradation, with IDOL homodimerization thought to be required for its activity. To probe the possibility of modulating LDLR levels with an inhibitor of IDOL homodimerization, we screened a SICLOPPS library of 3.2 million cyclic peptides for compounds that disrupt this protein-protein interaction. We identified cyclo-CFFLYT as the lead inhibitor, and improved its activity through the incorporation of non-natural amino acids. The activity of the optimized cyclic peptide was assessed in hepatic cells, with a dose-dependent increase in LDLR levels observed in the presence of our IDOL homodimerization inhibitor

Dataset for Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase

Raw data supporting: Leitch, E. et al (2018). Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase. Chemical Science. </span

Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells

Peer reviewe

Chromone: A valid scaffold in medicinal chemistry

Chromones are a group of naturally occurring compounds that are ubiquitous in nature, especially in plants. The word chromone is derived from the Greek word chroma, meaning “color”, which point out that many chromone derivatives can exhibit a diversity of colors.This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013). A.G. (SFRH/BD/43531/2008) and M.J.M. (SFRH/BD/61262/2009) thank FCT for grants