Development of stapled short helical peptides capable of inhibiting vitamin D receptor (VDR)-coactivator interactions

Yosuke Demizu; Saori Nagoya; Manami Shirakawa; Megumi Kawamura; Nanako Yamagata; Yukiko Sato; Mitsunobu Doi; Masaaki Kurihara

doi:10.1016/j.bmcl.2013.06.002

Development of stapled short helical peptides capable of inhibiting vitamin D receptor (VDR)-coactivator interactions

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4292-6. doi: 10.1016/j.bmcl.2013.06.002. Epub 2013 Jun 10.

Authors

Yosuke Demizu¹, Saori Nagoya, Manami Shirakawa, Megumi Kawamura, Nanako Yamagata, Yukiko Sato, Mitsunobu Doi, Masaaki Kurihara

Affiliation

¹ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. demizu@nihs.go.jp

PMID: 23806555
DOI: 10.1016/j.bmcl.2013.06.002

Abstract

We synthesized stapled helical leucine-based peptides (DPI-01-07) containing 2-aminoisobutyric acid and a covalent cross-linked unit as inhibitors of vitamin D receptor (VDR)-coactivator interactions. The effects of these peptides on the human VDR were examined in an inhibition assay based on the receptor cofactor assay system, and one of them, DPI-07, exhibited potent inhibitory activity (IC₅₀: 3.2 μM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoisobutyric Acids / chemistry
Binding Sites
Circular Dichroism
Databases, Protein
Humans
Nuclear Receptor Coactivator 2 / antagonists & inhibitors*
Nuclear Receptor Coactivator 2 / metabolism
Peptides / chemistry*
Peptides / metabolism
Peptides / pharmacology
Protein Interaction Maps / drug effects
Protein Structure, Secondary
Protein Structure, Tertiary
Receptors, Calcitriol / antagonists & inhibitors
Receptors, Calcitriol / metabolism

Substances

Aminoisobutyric Acids
Nuclear Receptor Coactivator 2
Peptides
Receptors, Calcitriol
2-aminoisobutyric acid