Disrupting the PCSK9/LDLR protein-protein interaction by an imidazole-based minimalist peptidomimetic

Org Biomol Chem. 2016 Oct 18;14(41):9736-9740. doi: 10.1039/c6ob01642a.

Abstract

Herein we report on the multicomponent synthesis of a novel imidazole-based compound, able to act efficiently as a minimalist β-strand mimic. Biological evaluation proved its ability to impair the LDLR-PCSK9 protein-protein interaction, disclosing it as the first small molecule exerting a PCSK9-mediated hypocholesterolemic effect.

MeSH terms

  • Hep G2 Cells
  • Humans
  • Imidazoles / chemistry*
  • Models, Molecular
  • Peptidomimetics / chemistry*
  • Peptidomimetics / pharmacology*
  • Proprotein Convertase 9 / chemistry
  • Proprotein Convertase 9 / metabolism*
  • Protein Binding / drug effects
  • Protein Conformation
  • Receptors, LDL / chemistry
  • Receptors, LDL / metabolism*

Substances

  • Imidazoles
  • Peptidomimetics
  • Receptors, LDL
  • imidazole
  • Proprotein Convertase 9