title: Structural development of stapled short helical peptides as vitamin D receptor (VDR)-coactivator interaction inhibitors.
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).
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors: Takashi
authors: T
authors: Misawa
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: demizu@nihs.go.jp.
authors: Yosuke
authors: Y
authors: Demizu
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Megumi
authors: M
authors: Kawamura
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors: Nanako
authors: N
authors: Yamagata
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: masaaki@nihs.go.jp.
authors: Masaaki
authors: M
authors: Kurihara
mesh_terms: D002942:Circular Dichroism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D018167:Receptors, Calcitriol
keywords: Helical structure; Protein–protein interaction; Stapled peptide; Vitamin D receptor