Structural development of stapled short helical peptides as vitamin D receptor (VDR)-coactivator interaction inhibitors

Bioorg Med Chem. 2015 Mar 1;23(5):1055-61. doi: 10.1016/j.bmc.2015.01.007. Epub 2015 Jan 12.

Abstract

We developed several stabilized helical heptapeptides (DPI-01-10) composed of l-leucine residues, an α,α-disubstituted α-amino acid (α-aminoisobutyric acid [Aib] or hydroxymethylserine [Hms]), and a stapled side chain as inhibitors of vitamin D receptor (VDR)-coactivator interactions. The inhibitory activity of these peptides against VDR-coactivator interactions was evaluated using a receptor cofactor assay system, and DPI-08 demonstrated strong activity (IC50: 3.2μM).

Keywords: Helical structure; Protein–protein interaction; Stapled peptide; Vitamin D receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Conformation
  • Receptors, Calcitriol / antagonists & inhibitors*
  • Receptors, Calcitriol / metabolism
  • Structure-Activity Relationship

Substances

  • Peptides
  • Receptors, Calcitriol